|Year : 2015 | Volume
| Issue : 5 | Page : 29-72
|Date of Web Publication||23-Nov-2015|
Source of Support: None, Conflict of Interest: None
|How to cite this article:|
. Posters. Indian J Nucl Med 2015;30, Suppl S1:29-72
| Cardiovascular Imaging|| |
The Impact of Appropriate Use Criteria 2013 on the diagnostic accuracy of SPECT-MPI
Deepanksha Datta, Narvesh Kumar, Nitin Yadav, Amit Kumar, Mudalsha Ravina, Sukanta Barai, Sanjay Gambhir
Department of Nuclear Medicine, Sanjay Gandhi Post Graduate Institute of Medical Sciences, Lucknow, India
Background and Aim: Appropriate Use Criteria have been developed by ASNC to aid in the optimal use of SPECT- myocardial perfusion imaging (MPI), a technique that is a mainstay of risk-assessment for ischemic heart disease. In this study, we have tried to evaluate the impact of appropriate use criteria on the diagnostic value of SPECT-MPI. The sensitivity, specificity and overall accuracy of SPECT-MPI is calculated under the appropriate category. Methods and Results - A retrospective study of 35 consecutive patients undergoing outpatient, community-based SPECT-MPI and Invasive coronary angiography was conducted. The maximum time-interval between the two tests was 30 days. Subjects were categorized as normal and abnormal SPECT-MPI. The abnormal MPI test includes presence of stress-induced ischemia or non-viable myocardial tissue. The normal MPI test consists of absence of stress-induced ischemia. In the appropriate category with positive coronary angiography results, positive or negative MPI occupied 82% and 18% respectively. In the appropriate criteria, the sensitivity, specificity, positive predictive value, negative predictive value and overall accuracy of SPECT-MPI is 82%, 50%, 96%, 14%, 80 % respectively. The likelihood ratio positive is 1.64, and likelihood ratio negative is 0.36. Conclusion: The Appropriate Use Criteria has a definite impact on the diagnostic accuracy of SPECT-MPI. There is high sensitivity, positive predictive value, diagnostic accuracy and likelihood ratio positive of SPECT-MPI when used in appropriate category.
Normal Limits for Left Ventricular Ejection Fraction and Volumes Determined by Gated SPECT: Comparison Between Cedars-Sinai Medical Center's QGS and Segami's CardioGam
8310 Guilford Rd, Columbia, MD 21046, United States
Background and Aim: Several gated SPECT processing software are available in the market however, due to the difference in the left ventricular modelling and methods of myocardial definition, the results are substantially different. Therefore it is necessary to define normal limits specific to each software and understand the reason for their differences to adequately interpret individual cases. The aims of this study were to define normal limits of ventricular volumes and ejection fraction for Cedars-Sinai's QGS and Segami's CardioGam software and to evaluate the relationships between the results. Materials and Methods: QGS, developed at Cedars Sinai Medical Center LA, is an automatic gated SPECT processing software operating in 3-dimensional space, based on asymmetric Gaussian fitting of count profiles across the myocardium and identification of endo and epicardial surfaces. In CardioGam, developed by Segami in collaboration with Stanford University, the location of the myocardial wall is defined by statistical parameters and not by edge detection. The algorithm operates in a 3-dimensional space and determines the center of myocardial wall, which location is defined as the center of gravity of each activity profile plotted from the center of left ventricular cavity outward. This method has been validated against planar equilibrium radionuclide angiography. Patient population: A total of 173 healthy subjects (91 women, mean age 44 years). Acquisition: 30 mins after injection of 1110 MBq of 99mTc-sestamibi at peak exercise Studies were reconstructed and reoriented with AutoSPECT plus then processed with both QGS and CardioGam for determination of End diastolic (EDV), end systolic (ESV) and Left Ventricle Ejection fraction (LVEF). Results: The mean ejection fraction was similar between the methods but the volumes and cardiac output were significantly lower for QGS than CardioGam. QGS lower limit for LVEF was 43% for men and 51% for women compared to 49% and 53% respectively for CardioGam. Conclusion: QGS has been reported to underestimate ventricular volumes and consequently overestimate LVEF. This explains the low cardiac output values observed with this method and the trend in ejection fraction differences. CardioGam gave higher volume values (diastolic and systolic) and consequently higher stroke volumes and cardiac output results. In spite of the trend observed, mean ejection fraction results were similar. Given the differences between the techniques, it is necessary to apply different normal limits for each software and consider these factors when interpreting individual cases.
| Cerebrovascular Imaging|| |
Role of SISCOS (Substraction Ictal SPECT Coregistered to Inter-Ictal Spect) in Lateralization and Localization of Epileptogenic Foci in Patients with Intractable Epilepsy
Anshul Sharma, Nishikant Damle, Madhavi Tripathi, Deepak Aheer, Chandra Shekhar Bal
Deptartment of Nuclear Medicine, All India Institute of Medical Sciences, New Delhi, India
Background and Aim: Intractable epilepsy responds poorly to anti-epileptic medications. However those patients in whom, a single epileptogenic focus can be identified, may be considered for a surgical intervention. SISCOS can help identify active epileptogenic foci and also rule out multiple foci in patients being considered for surgery. Materials and Methods: Imaging data (ecd -ictal and inter-ictal) of 102 consecutive patients(71 MALE AND 31 FEMALES with average age 14.9 yrs) with intractable epilepsy was evaluated with SISCOS. with a filter setting between 2sd and 5sd, the likely foci were identified by two nuclear medicine physicians and were characterized into localized(single or contagious), lateralized(multiple but non contiguous) and non-localized. these results were compared with previous reports given to these patients, which were given after detailed evaluation of ictal, inter-ictal images along with other evidences (MRI, semiology, EEG). Results: After image analysis right sided involvement was found in 40 patients, left in 43, bilateral in one.of these 84 patients, in 59 we could find a definite focus and in rest 25 we were only able to lateralize to one side (owing to multiple foci).no definite localisation or lateralisation could be ascertained in 18 patients. agreement with old reported data was found to be 80/102. Conclusion: SISCOS was able to ascertain likely epileptogenic foci in 82.4% of patients with definite single focus in 50%.
Metabolic Imaging with FDG PET in Motor Neuron Disease
Abhishek Khare, Indirani M, Shilpa Kalal, Shelley S
Department of Nuclear Medicine and PET/CT, Apollo Hospitals, Chennai, Tamil Nadu, India
Background and Aim: Motor neuron diseases (MND) are a rare group of progressive neurodegenerative disorders that destroy motor neurons, which are responsible for voluntary muscle activity such as speaking, walking, breathing, and swallowing. Based on involvement of Upper motor neurons (UMN) or lower motor neurons (LNM) or both, these diseases are classified into 5 subtypes; amyotrophic lateral sclerosis (ALS) , primary lateral sclerosis (PLS), progressive muscular atrophy, Progressive bulbar palsy and pseudobulbar palsy. Diagnosis of MND requires clinical, electrophysiological studies and lab/genetic testing. Molecular imaging with 18F-2-fluoro-2-deoxy-D-glucose positron emission tomography (FDG PET) may give useful insight into the underlying pathophysiology of the disease. Materials and Methods: 6 patients with clinical diagnosis of motor Neuron disease (4 ALS and 2 PLS) underwent FDG PET brain scans. PET scans were done as per society of nuclear medicine procedure guidelines for FDG PET brain imaging. Images were acquired on Philips Gemini 64 slice PET/CT with Time of flight technology 45 min. after injection of radiotracer with CT based attenuation correction. Visual as well as quantitative analysis was done using NeuroQ™analysis software. Discussion: There are few studies on the role of brain FDG-PET scans in MND. A review of literature reveals ALS patients seem to have diffuse cortical hypometabolism, involving mostly the frontal lobes, motor cortices, anterior temporal regions with cingulate gyri involvement. When ALS is associated with frontotemporal dementia (FTD), extensive temporal hypometabolism is often seen in addition to severe diffuse frontal hypometabolism. In PLS FDG-PET imaging reveals additionally primary motor cortex hypometabolism. Midbrain hypermetabolism has also been reported in few studies. Conclusion: Hypometabolism was predominantly seen in fronto-temporal, posterior cingulate and primary motor cortex region in ALS, while in PLS significant primary motor cortex hypometabolism (stripe sign) was predominant finding. Our findings though in a small sample were consistent with those in published literature. FDG PET imaging with typical metabolic patterns, may serve as an important imaging biomarker to support a differential diagnosis of MND.
Oasis - SISCOM with MIRegister
8310 Guilford Rd, Columbia, MD 21046, United States
Background and Aim: Since mutual information-based registration was proposed by Viola and Wells in 1994, a number of multi-modality implementation have been discussed. The aims of this paper is to demonstrate two Oasis applications- namely MIRegister and SISCOM to find precise seizure focus in the brain of epileptic patients with the help of SPECT and MRI images acquired on separate equipment. Materials and Methods: MIRegister, an Oasis application to automatically register medical data volumes from the same or different modalities, based on a normalized mutual information algorithm. MRI is the investigation modality of choice in patient with epilepsy as T1,T2 and flair images are crucial in increasing the conspicuity of otherwise undetectable lesions. SPECT, a nuclear medicine imaging technique based on the knowledge of seizures causing increased ictal region cerebral perfusion and decreased interictal perfusion. A side-by-side visual analysis of ictal and interictal SPECT images has limitations (doesn't account for differences in injected dose, tracer decay) and is subjective (user-dependent). Hence registration and fusion of the SPECT images with MRI is performed. Use of MRI improves the sensitivity and specificity of SPECT. Results: SISCOM application provided a snapshot of the cerebral blood flow patterns during seizure and showed areas of hypoperfusion in the region of seizure focus in between seizures (rest). The MIRegister user interface allows for the control of parameters, such as thresholds for cortical activity, FOV necessary to accomplish the registration. The application also created a fused representations of regions of focal activation with the structural information of the MRI. The fused set of images provided for visual inspection of the accuracy of registration. The fused representations can be controlled by using the alpha-blending tool to review more or less of the SPECT and MRI image. Conclusion: The algorithm is pixel intensity based (no need for anatomical landmarks) and therefore can be used for any combination of modalities (SPECT, PET, CT, MRI) and is applicable to all body parts (e.g., Lung, Abdomen, Head/Neck). CT and MRI could be a separate/independent acquisition. Several hybrid scanners (e.g., PET/MR), very expensive with long acquisition times, are upcoming and in the nascent stage. However, an equally effective and low-cost multi-modality software solution might be the practical solution proving boon to both patients and clinicians. Oasis PET-CT registration/fusion for lung tumor detection, PET-CT-MR for function and localizing brain lesions and PET-MR fusions for prostate cancer are just a few other applications in Oasis.
| Correlative Imaging|| |
Evaluation of 68 Ga-chloride as an infection imaging agent in comparison with 99m Tc- labelled leucocytes and cell culture sensitivity
Amritjyot Kaur, Jaya Shukla, Bhagwant Rai Mittal, Sarika Sharma, Baljinder Singh
Department of Nuclear Medicine and PET, Postgraduate Institute of Medical Education and Research, Chandigarh, India
Background: 68 Gallium have similar chemical characteristics as 67 Gallium which can bind to transferrin and is transported to the inflammatory site. At inflammatory site, neutrophils release large amounts of lactoferrin. Ga-68, with a higher binding affinity for lactoferrin than transferrin, localizes at the site of inflammation by dissociating from transferrin and binding to lactoferrin. Aim: (i) Preparation and quality control of 68 Ga-chloride (ii) Compare 68 Ga-Chloride and 99m Technetium -HMPAO labelled leukocytes results with cell culture sensitivity. Materials and Methods: Nineteen adult patients (16M: 3F; Age: 20-65years) with painful prosthesis and diabetic foot clinically suspicious of infection were enrolled for the study. Nineteen patients were subjected to 68 Ga-chloride scan and seventeen out of this underwent 99m Tc-HMPAO labeled leukocyte imaging. Cell culture sensitivity test reports were available for 13 patients.15-20mCi 99m Tc-HMPAO Labeled leukocyte is injected and Whole body and Static images were Acquired at 1 hr, 4 hr and 24 hr and tomo acquisition at 4 Hrs after injection. 68 Ga-chloride eluted from ITG Ge-68/Ga-68 Generator with 0.1 HCl. pH was adjusted to 6 with the help of acetate buffer and passed through 0.22 um membrane filter. Quality control was done by ITLC using sodium citrate as mobile phase. PET/CT Images were acquired 1.5 to 2 hrs after 5-8 mCi of Gallium-68 Chloride to increase target to background ratio and for increased focal uptake at site of infection. Results: The labelling yield of 99m Tc-HMPAO labelled leukocytes was between 70-96%. Radiochemical purity of 68 Ga-chloride by ITLC was 100%.Culture sensitivity was taken as gold standard. 68 Ga-Chloride results are compared with culture Sensitivity results for 13 patients .On the other hand, when Tc-99m HMPAO labelled leucocytes scan results for 11 patients were compared with culture sensitivity as gold standard. The Sensitivity, Specificity, Positive Predictive value and Negative Predictive value of 68 Ga-chloride PET/CT imaging in patients with suspected bone infections was 100%, 60%, 80% & 100%, respectively. The Sensitivity and Specificity, Positive predictive value, Negative Predictive value for 99m Tc-HMPAO labelled leukocytes was 50% and 100%, 100% and 62.2% respectively. Conclusion: Thepresent study demonstrated that 68 Ga-chloride PET have better spatial resolution, higher sensitivity, and possibility for quantitative assessment of tracer accumulation in tissues, and lower absorbed radiation dose for the study subject. Study with large population size is required to establish Gallium -68 chloride as a promising radiopharmaceutical for infection imaging.
| Gastro Intestinal Imaging|| |
Method developed for estimation of Orocaecal transit time for Non-cirrhotic and cirrhotic portal hypertension
Managala Ghorpade*, Suruchi Shetye*, Rasna Tiwari*, Shobna Bhatia, Akash Shukla, Kiran S. Shwetal Pawar*, G H Tilve*
Department of Nuclear Medicine*, Department of Gastroenterology, Seth G S Medical College and KEM Hospital, Mumbai, India
Background and Aim: To develop the technique of calculation of orocaecal transit time, and to compare it time between patients of NCPH with cirrhosis and controls. Materials and Methods : Patients with NCPH (n=10) or cirrhosis of liver (n= 30), who were referred to our department for the orocaecal transit study, were considered for the study. 28 controls were selected from the patients with normal gastric emptying and ruling out any or hepatosplenic portal pathology. Liquid scintigraphy was chosen, as it more reproducible, easy one-day protocol with less radiation exposure to subject. After taking relevant history, such as prior surgical procedures and current medications, patient was prepared for study. On day of study, the subject was asked to ingest radioactive labeled water (250-350ml) with 1 mCi 99mTc-sulfur colloid. A marker was placed in right iliac fossa at Mcburney's point for anatomical terminal ileum demarcation. The static images were acquired in anterior and posterior projection for 6 hours, at 1hr interval. This was followed by static image at 24 hours. Geometric mean and decay corrected counts were used to calculate percentage of activity passing through terminal ileum based on ROI method.If more than 40% of the total abdominal Tc99m counts administered had moved through the small bowel into the terminal ileum or colon at the end of 4 hours (>240 min), small-bowel transit was considered as normal. The relationship between small bowel delayed motility and portal hypertension is expected in cases of NCPH, cirrhosis but not in controls. Results : The orocaecal transit time was mean 180 min (SD 76 min) in controls, 413 min in cirrhosis and in 236 NCPF. Out of total 10 patients of NCPH, 8 patients show delayed orocaecal transit time i.e 80%. Out of total 30 patients of Cirrhosis 60% patient show delayed transit time. Conclusion : The orocaecal transit time was calculated by using the Tc-99m Sulfur colloid as an easy method by using single day protocol. It was found to be delayed in non-cirrhotic and cirrhotic portal hypertension.
Value of RBC scan in unexplained GI Bleed and role of capsule endoscopy
N.Parvathinathan 1 , S.Lavanya 1 , Balkis Begum 1 , G.Rangarajan 1 , N. Anandi 1 , R.KrishnaKumar 1 , G.Selvaluxmy 2 , A.S.Ramakrishnan 3
Cancer Institute (W.I.A) Chennai, Tamil Nadu, India
Background and Aim: RBC scan in unexplained GI Bleed locates the site and further localization is done with Capsule endoscopy in small bowel disease. Materials and Methods: A 61 years old female had synchronous malignancy of Adenocarcinoma of splenic flexure of colon and squamous cell carcinoma of uterine cervix stage II B. Patient had left hemicolectomy and following surgery she was treated with 6Mv x-ray beam to pelvis upto 66Gy with weekly cisplatin with paraaortic radiation upto 50 Gy followed by intracavitary radiation. The patient was treated with 6 cycles of xelox chemotherapy subsequently. 6 months later patient developed complaints of malena. Management: On evaluation, hemoglobin was 6g/dl and packed red cell transfusions were given. Upper GI endoscopy was within normal limits. Stool for occult blood - positive. Colonoscopy revealed radiation proctitis. Tagged RBC Scan - 2mg of SnCl2 is dissolved in 2ml normal saline and 1ml of SnCl2 is injected intravenously and 20minutes later sodium pertechnate 25mCi was given to label RBC. Initially dynamic images of the abdomen and pelvis (anterior and posterior) were acquired @ 1sec/frame for 1minute and 1minute/ frames for 30minutes. Later static images were acquired at 2, 4, 6 and at 24 hours. It showed increased uptake in right hypochondrium region below the liver and the 24 hours imaging also showed increased uptake in same site. Capsule endoscopy was done and it revealed chronic radiation enteritis in jejunum and ileum. No bleeding sites were noted in large bowel. The patient was conservatively managed. Conclusion: Tagged RBC scan is helpful in locating the unexplained GI bleed and it is a roadmap for further localization of the site especially in small bowel with capsule endoscopy. This is to highlight the combination is very useful.
Multifocal Epithelioid Angiosarcoma of the Stomach withliver metastasis - A Case Report
Hemant Sachani, Noaline Sinha
Department of Nuclear Medicine, Artemis Hospitals, Gurgaon
0Background and Aim: Angiosarcoma is a malignant vascular tumor that originates from the mesenchymal cells that have undergone angioblastic differentiation. Multifocal Epithelioid angiosarcoma is a very rare malignant, vascular neoplasm and even more so in the gastrointestinal tract. With only individual case reports scattered throughout the literature with the primary in the stomach, where its distinction from adenocarcinoma may be extremely difficult. Case Presentation: We report an F-18 fluorodeoxyglucose (FDG) positron emission tomography (PET)/CT scan in case of a metastatic multifocal epithelioid angiosarcoma of the stomach in a 29-year-old woman who presented with abdominal pain and was found to have multiple liver nodules on CT scan suggestive of a tubercular lesion or a lymphoma. PET CT scan was performed according to institute protocols. The images revealed a large FDG avid well defined well marginated heterogeneously enhancing predominantly exophytic mass with a maximum SUV (standardized uptake value) of 20.2 and multiple FDG avid liver metastases. The patient underwent a distal gastrectomy with gastro-jejunostomy and entero-enterostomy and a blackish brown growth measuring 5.0 x 5.0 x 4.0 cm was found on the lower end of the greater curvature. Histologically, the sections showed multifocal lesions involving full thickness of the stomach wall, composed of large, plump, polygonal to spindle cells lining haphazard, anastomosing channels, with patchy solid growth pattern and rudimentary lumen formation with the cells showing epithelioid features. Those neoplastic cells stained positive for CD31, CD34, and factor VIII-related antigen. These findings confirmed the diagnosis of primary gastric epithelioid angiosarcoma. Discussion: We highlight the potential of fluorine-18 fluorodeoxyglucose positron emission tomography/computed tomography as an important diagnostic tool in the evaluation of this tumor and thus contribute to the existing sparse literature on this fascinating yet devastating disease. Conclusion: Multifocal epithelioid Angiosarcoma of stomach being rare entity and a morphological mimic of more common entity of adenocarcinoma needs careful evaluation and often immunohistochemical findings for accurate diagnosis.
Role of F-18 FDG PET-CT in staging of patients with tongue cancer: An experience at a single tertiary care center
Tarun Kumar Jain 1 , Rajender Kumar Basher 1 , Anish Bhattacharya 1 , Jayamanti Bakshi 2 , Bhagwant Rai Mittal 1
1 Department of Nuclear Medicine, Post Graduate Institute of Medical Education and Research, 2 Department of ENT, Post Graduate Institute of Medical Education and Research, Chandigarh, India
Background and Aim: To evaluate the diagnostic and prognostic performance of contract enhanced F-18 FDG PET/CT in staging of tongue carcinoma. Materials and Methods: We retrospectively analyzed 33 patients (4 females and 29 males; age range 28-78 years; mean age 50.75 years) of carcinoma tongue, who underwent F-18 FDG PET/CT. All the patients, included in this study had histopathological diagnoses of tongue cancer and received no treatment. Whole body FDG PET/CT was done for initial staging as well as for detection of distant metastasis. Scans were analyzed by two expert nuclear medicine physicians and any abnormal FDG uptake was correlated with lesion on CECT and taken as positive. The results were compared with the reference standard using histopathology (if available), clinical and imaging follow up. Results: Clinically tongue ulceration was noticed in twenty one (63.6%) patients, tongue swelling in seven (21.2%), neck swelling in three (9.1%) and dysphagia inone (3%). FDG PET/CT identified the primary lesion in all 33 patients with additional locoregional lymphnodes and distant metastatic lesions in 22 (15%) and 6 (18%) patients respectively. On lesion based analyses in 6 patients with distant metastases, isolate or combinedly FDG PET identified lymph nodes, lung and skeletal metastases in 3, 3 and 1 patients respectively. All the patients were treated either by surgery, radiotherapy or chemotherapy. FDG PET /CT changed the management in 6 (18%) patients by identifying distant metastases. We also noted that there was no correlation between SUV max and patient survival (Pearson's coefficient rank correlation, r=-0.000;P=1.000). Conclusions: We concluded that 18F-FDG PET/CT helped in identification of additional sites of metastatic involvement, upstaging and further management. Similarly we also conclude that FDG uptake (SUVmax) had no correlation with patient survival.
| Immunology|| |
Skull base osteomyelitis: rejuvenating Galium-67 citrate infection imaging in current era
Preeti Singh, Shwetal Pawar, Mangala K. Ghorpade,
G. H. Tilve
Department of Nuclear Medicine and PET-CT, Seth G.S. Medical College and KEM Hospital, Mumbai, India
Background and Aim : To evaluate the role of Ga-67 citrate scintigraphy and its implications in the management of skull base osteomyelitis. Materials and Methods : The data was collected both retrospectively and prospectively from the period of February 2012 to August 2015. 2-4 mCi of Ga-67 citrate was administered i.v. and delayed 24 hours planar imaging was acquired with regional SPECT-CT. 14 (n=14) patients were studied during this period. 1/14 had a negative Ga-67 citrate scan.13/14 had positive Ga-67 citrate scan for skull base osteomyelitis. 9/13 with positive scan findings had follow up scans. These patients with skull base osteomyelitis were followed up clinically. Results : 9/13 (13 with positive findings for skull base osteomyelitis) patients had baseline scan and follow up scan after the start of course of antibiotics for status quo. All 4 who didn't come for follow up scan had scan finding in favor of skull base osteomyelitis. 8/9 patients underwent 2 scans and 1/9 had 5 scans in total over 9 months. In all patients with skull base osteomyelitis the management was influenced by the gallium 67-citrate imaging along with response to anti-biotic treatment. Clinical correlation was established with decrease in symptomatology and follow up scan finding into categories of complete/partial or no change as response. 77.7% (7/9) showed partial response with residual uptake at the site of query. 11.1% (1/9) showed no change in scan findings and symptomatically. 11.1% (1/9) showed complete resolution with absence of tracer uptake at the involved site of skull base. Conclusion : Gallium 67-citrate imaging played a very important role in management of skull base osteomyelitis in diagnosing and in assessing response to anti-biotics. It was however not used to assess the end point to stop the anti-biotics, which was decided on the basis of symptomatology.
Use of recombinant bacteriophage, displaying single domain antibody (SdAb) against thyroglobulin (Tg), in an IRMA system to measure serum Tg
J.Kumarasamy, Savita Kulkarni, Chandrakala Gholve, Archana Damle, M. G. R. Rajan
Radiation Medicine Centre, BARC, TMH Annexe, Parel, Mumbai - 400 012, India
Background and Aim: To evaluate an IRMA using recombinant bacteriophage displaying single domain antibody (SdAb) against thyroglobulin (Tg) as a capture antibody. Materials and Methods: Bacteriophage displaying SdAb against human Tg was produced at RMC. The phage showed good immunoreactivity to Tg which could be used as substitute for monoclonal antibody. Solid-phasing of the phage to polystyrene tubes was carried out and tested, but showed insufficient binding capacity. Hence, magnetic particles as the solid phase was tried out and this gave satisfactory results due to the large surface area available. The coupling was facilitated by 1,1'-Carbonyldiimidazole (CDI). 125- I labelled monoclonal antibody (in-house produced) was used as a tracer. Totally 25 serum samples were analyzed for Tg using this system. Results: The phage displaying the recombinant SdAb against Tg, coupled with magnetic particle was able to bind Tg in dose dependent manner. The Tg values in serum samples obtained were comparable to values detected by routine Tg IRMA assay used in the laboratory [ y(Phage Mag - IRMA) = 0.23Tg-Ab-IRMA + 10.4, r=0.82]. These are preliminary results and further optimization is in progress. Conclusion: The cellulose magnetic particle is a better alternative to polystyrene tubes for solid-phasing of large SdAb phage particles. The phage retained its immunoreactivity in Tg-IRMA system.
| Invitro Nuclear Medicine|| |
Camptothecin enhances 131 I-rituximab-induced cell death in Raji cells entailing MAPK pathways
Chandan Kumar 1 , Grace Samuel 2 , S. A. Khan 2 and Sharmila Banerjee 1
1 Radiopharmaceutical Chemistry Section, Radiochemistry and Isotope Group, 2 Isotope Production and Applications Division,Bhabha Atomic Research Centre, Mumbai - 400 085, India
Background and Aim: Non Hodgkin's lymphoma (NHL) is a clinically heterogeneous group of hematological malignancies arising from B, T or NK-lymphoid cells with more than 90% originating from the B-cells only. Most of the B-cell malignant tumor expresses a high number of CD20 receptors, making it one of the possible targets for therapy of NHL. There are various modalities available for therapy of NHL, such as chemotherapy, radiation therapy, immunotherapy and radioimmunotherapy. Amongst various monoclonal anti CD20, Rituximab, an immunotherapeutic of chimeric origin has been approved by FDA for clinical use in 1997 and is available at reasonable cost after the expiry of the patent. Though, rituximab is used for treatment of NHL patients, it has found that only 50 % patients show clinical response to Rituximab and found that mitogen activated protein kinase (MAPK) play an important role in response to therapy and cell proliferation. To enhance the efficacy of Rituximab in B-cell lymphoma, it was labelled with Iodine-131 and its effect was assessed on Raji cells in combination with camptothecin (CPT). CPT binds to the topoisomerase I-DNA complex which causes DNA strand breaks upon replication leading to cell death. A combination of various therapeutic modalities for NHL was envisaged to have not only an enhanced effect but also mitigate the limitations of each therapeutic modality. Herein, the studies on Raji cells treated with 131 I-rituxiamb in combination with CPT, exploring the efficacy of treatment and the underlying mechanism necessary for the cell death is being reported. Material and Methods: Raji cells were pre-incubated with CPT, (250 nM) for 1 h followed by incubation with 131 I-rituximab (0.37 and 3.7 MBq) upto 24 h. Cells were harvested after 24 h, washed and cellular toxicity, apoptosis and expression of proteins related to cell death and MAPK signaling pathway were investigated. Results : It was found that the 131 I-rituximab in combination of CPT showed the highest cell toxicity and extent of apoptosis compared to respective controls. Anti-apoptotic protein (bcl xl ) and pro-apoptotic protein (puma) expressions were down-regulated in the combination treatment protocol using CPT (250 nM) and 131 I-rituximab. The basal level of expression of ERK1/2 and p38 were found to decrease in the combination treatment of CPT and 131 I-rituximab. The phosphorylation of p38 increased while phosphorylation of ERK1/2 decreased in Raji cells treated with a combination of CPT and 131 I-rituximab. Conclusion: The results showed that presence of CPT has beneficial effect on 131 I-rituximab-induced cell death in B-cell lymphoma. The results further suggest that CPT has the potential to sensitize 131 I-rituximab induced cell death in Raji cell line involving MAPK signaling pathways.
Storage conditions for reconstituted HMPAO effectsradiochemical purity of 99m Tc-HMPAO
Mahesh Rao a , Rozy Kamal a ,Vijayta D.Chadha a , D. K. Dhawan b
a Centre for Nuclear Medicine, b Department of Biophysics, Panjab University, Chandigarh, India
Background and Aim: The unusual in vitro instability of 99m Tc-HMPAO is considered a major disadvantage as the labeled product must be injected within 30 minutes of reconstitution of HMPAO vial. In the present studies it was our interest to check whether HMPAO once reconstituted could be radiolabeled later with sufficient efficiency when stored at appropriate storage conditions. Materials and Methods: Changes in %labelling efficiency for 99m Tc-HMPAO, following storage of reconstituted HMPAO at different temperatures (-20 to +20C)for different storage time (day zero to day 21 of storage), with and without augmentation of stannous chloride, during radiolabeling was invetigated. Results: The percentage of primary 99m Tc-HMPAO on day 1 of storage of fractionated HMPAO at -20°C was greater than 80% which is considered suitable for brain uptake studies. The percentage decreased to 46 and 49 following storage at 4°C and 20°C respectively. Further,percentage of primary 99m Tc-HMPAO was found to be maximum on the day of preparation i.e. day zero of storage and decreased constantly with time till Day 21. Similar pattern was observed on subjecting the fractionated HMPAO to different storage temperatures or on addition of stannous chloride during radiopharmaceutical preparation. Conclusion: It can be concluded that HMPAO when stored at -20˚Cafter re-constitution can be radiolabeled with>80% radiochemical purity, upto 24 hours. Further stor age after 24 hours at any temperature, or augmentation with stannous chloride does not improve the radiochemcal purity of 99m Tc-HMPAO.
| Molecular Imaging|| |
N 4 vehicle based acetamidobenzoxazolone derivative for imaging of Translocator Protein (18 kDa) during inflammatory condition
Neelam Kumar, 1,2 Pooja Srivastava, 2 Sunita Bhagat, 1, * AnjaniK Tiwari 2, *
1 Organic Synthesis Research Laboratory, Department of Chemistry, A.R.S.D. College, University of Delhi, New Delhi-110021, 2 Division of Cyclotron and Radiopharmaceutical Sciences, Institute of Nuclear Medicine and Allied Sciences, Delhi, India
Background and Aim : Development of radio-ligand for Translocator Protein [18 kDa, TSPO] to study its role in activation of glial cells in the injured brain as well as in inflammatory condition, is one of the most critical issues of biomedical imaging. It has found that TSPO expression is markedly upregulated in such inflammation conditions and easily correlated to the extent of microglial activation, making the quantification of TSPO density a standard indicator for brain diseases. Here we have synthesized a new molecule 2,2',2''-(10-(2-((3-(2-(methyl(phenyl)amino)-2-oxoethyl)-2-oxo-2,3-dihydrobenzo[d]oxazol-5-yl)amino)-2-oxoethyl)-1, 4, 7, 10-tetraazacyclododecane-1, 4, 7-triyl)triacetic acid (MPAOT) labeled with 99m Tc and evaluated in vitro as well as in vivo for imaging of TSPO expression. Materials and Methods: MPAOT was synthesized by easily reproducible methods and radiolabelled with 99m Tc in nine steps. To determine specific binding of this compound with TSPO ischemic model of rat was used. Results: The MPAOT ligand was successfully synthesized and fully characterised by different techniques (FTIR, NMR and HRMS). 99m Tc-MPAOT was synthesized with a radiochemical purity of 98%. Biodistribution studies confirmed high accumulation of radioactivity in the TSPO-rich organs like lungs, heart, kidney and adrenal glands. The in vitro and in vivo binding patterns were firmly supported by difference in the contrast of radioactivity between ipsilateral and contralateral sites in rat images. Blocking experiments with unlabelled TSPO specific ligands MPMB or (PK11195) minimized the difference in uptake between the two sides. Conclusion: The present data shows that 99m Tc-MPAOT may act as a imaging marker for TSPO.
Diagnostic utility of an indigenously developed single vial ready to label kit preparation of 99mTc-Methionine for the detection of recurrent/remnant glioma-A cost effective substitute for the PET Imaging
Nisha Rani, Baljinder Singh, Narendra Kumar, Sarika Sharma, Ankit Watts, Puja P. Hazari, Sameer Vyas, Anish Bhattacharya, and Anil K. Mishra
Institute of Nuclear Medicine and Allied Sciences, Defence Research and Development Organisation, Delhi, India
Background and Aim: To evaluate the diagnostic utility of bis-methionine-DTPA (99mTc-MDM) and its comparative evaluation with contrast-enhanced magnetic resonance Imaging (ceMRI) and 18F-fluorothymidine-PET (18F-FLT-PET) for the detection of recurrent/residual glioma. Material and Methods: This prospective study included 36 patients (24M: 12F, mean age= 42.8 ±16.02yrs; range=8-72 yrs) having post-operative clinical suspicion of recurrent/residual glioma (23- Glioblastoma Multiforme-G-IV; 05-Astrocytoma/Oligodendroglioma-G-I/G-II; 05-Anaplastic Oligodendroglioma/Oligoastrocytoma-G-III; 03-Pilocytic astrocytoma-G-I) referred for 99mTc-MDM-SPECT and ceMRI, at PGIMER, Chandigarh. 99mTc-MDM-SPECT and ceMRI was done in 34 patients after radical radiotherapy (RT) (54.0-60.0 Gy) with or without concurrent temozolomide and one patient was followed at 3-months. Sixteen (16/36) patients underwent F-18-FLT-PET and two underwent C-11-methionine PET. Two patients were underwent 99mTc-MDM-SPECT and ceMRI before RT and one patient also underwent 99mTc-MIBI SPECT. Results: The present study used 99mTc-MDM kits preparations with mean radio labeling efficiency of 97.0± 1.5 %( n=40). MDM SPECT and ceMRI finding were concordant in 30 patients (15 positive & 15 negative). The findings were discordant in remaining 7 patients, with positive ceMRI & negative MDM-SPECT in 3- scans and negative ceMRI & positive MDM-SPECT in 4-scans respectively. We observed positive 99mTc-MDM-SPECT, 18F-FLT-PET and ceMRI scan findings in 9/16 and negative in 5/16 patients respectively. In the remaining 2of 16 patients, both 99mTc-MDM-SPECT and 18F-FLT-PET were positive but ceMRI was negative and we also observed in one patient of discordant findings that both 99mTc-MDM-SPECT and 99mTc-MIBI-SPECT was positive but ceMRI was negative for the evidence of recurrent/remnant disease. In the detection of recurrent/residual disease 99mTc-MDM-SPECT showed overall sensitivity, specificity, PPV, NPV and DA of 84.21%, 82.35%, 84.21%, 82.35% & 83.3% respectively. Conclusion: Methionine localized in brain tumors through uptake by amino-acid transport (LAT-1) mechanism. The diagnostic utility of 99mTc-MDM-SPECT imaging was comparable with that of ceMRI, 18F-FLT-PET and 99mTc-MIBI-SPECT found to be reliable in discriminating necrosis versus residual tumor. The development of amino-acid based 'SPECT' radiotracers may offers an economical and reliable substitute to 11C-methionine-PET imaging may be special interest in peripheral hospitals/developing countries not having access to expensive PET/cyclotron technology. However, long-term follow-up will be useful to support the diagnostic accuracy of the tracer.
Can Lu-177-trastuzumab be used as radioimmunotherapeutic agent for HER2/neu breast cancer?
Priya Bhusari, Jaya Shukla, Rakhee Vatsa, Madan Parmar, *Gurpreet Singh, **Amanjit Bal, ***Devinder K Dhawan, Bhagwant R. Mittal
Department of Nuclear Medicine and PET, *General Surgery, **Histopathology, PGIMER, Chandigarh, ***Centre for Nuclear Medicine, Panjab University, Chandigarh, India
Background and Aim: HER2/neu expressing is the most aggressive type of breast cancer and is associated with poor prognosis. About 30 % of all breast cancers express HER2/neu receptor protein. Trastuzumab (commercially available as Herceptin) is FDA approved monoclonal antibody that targets HER2 receptor. This study aimed at studying the receptor targeting and distribution of the radiopharmaceutical Lu-177-trastuzumab for use as radioimmunotherapeutic agent for targeted radionuclide therapy of HER2 breast cancers. Materials and Methods: Trastuzumab was radiolabeled with Lu-177 via conjugation with the bifunctional chelator DOTA. The conjugated trastuzumab was characterized using SDS electrophoresis and MALDI mass spectrometry. Purified conjugated trastuzumab was radiolabeled with Lu-177. The quality control of purified Lu-177-trastuzumab included the determination of radiochemical purity, stability, sterility pyrogenicity and immunoreactivity. The feasibility study in patients was approved by the institutional ethics committee. Two HER2 and two ER/PR positive negative metastatic breast cancer patients were enrolled for the study. Immunohistochemistry data was obtained to ascertain the HER2 status of the disease. 555 MBq Lu-177-trastuzumab was administered intravenously to all patients and imaging was performed at day 1, 5 and 7 post administration. The uptake of Lu-177-trastuzumab in the primary and metastatic sites was assessed. Results: Radiolabeling yield for Lu-177-trastuzumab varied from 76-91 %. The product was sterile and endotoxin content ranged between 73-113 EU/V. The conjugation did not hinder the immunoreactivity of trastuzumab as assessed by competition radioimmunoassay. Uptake of Lu-177-trastuzumab was observed in primary tumors in both patients (HER2 +ve) and metastatic sites on whole body images. SPECT-CT imaging showed good localization of the tracer in the metastatic sites in all the patients. However no uptake in primary as well as metastatic sites was observed in ER/PR positive but HER2 negative patients. Conclusion: This preliminary study suggests that Lu-177-trastuzumab may have the potential to be used as radio-immunotherapeutic agent for treatment of HER2 positive metastatic breast cancer.
F-18 FDG PET -CT in Immunoglobulin G4 related disease (IgG4 RD) - A rare case with rare presentation
Shilpa Kalal*, M Indirani, S Shelley, Abhishek K, Sibu
Department of Nuclear Medicine and PET-CT, Apollo Hospital, Chennai, Tamil Nadu, India
Background: Use of F18 FDG PET -CT for oncological purpose is well known. But diseases which are non oncological and non granulomatous are less evaluated with F-18 FDG PET -CT. A gentleman was evaluated for dysphagia and diagnosis of IgG4-RD was done based on histopathology. He was further evaluated with PET-CT scan. Case Description: 30 yrs old gentleman with no co-morbid conditions presented with dysphagia for 1 month duration. CT scan raised possibility of inflammatory pseudotumor of the right carotid sheath. Patient underwent open biopsy and HPE showed Fibrosis with lymphoplasmacytic and histiocytic infiltrates. IHC suggested CD68+ve, IGG+ve (background staining present) , IGG4 +ve (upto 40 cells/hpf focally). IGG4/IGG ratio 20-30%. Patient was referred for 18F-FDG PET/CT to look for the multiorgan involvement. After getting informed consen baseline PET-CT was performed. Images were acquired on Philips Gemini 64 slice PET/CT with Time of flight technology 45 min after injection of tracer with CT based attenuation correction. The lesions were described based on PET and CT findings both qualitatively and quantitatively.Baseline PET-CT showed metabolically active circumferential wall thickening of the descending aorta (at D5-D6 and D9-D10 vertebral levels) , lesion in the right carotid space, soft tissue deposits along the anterior chest wall eroding the sternum and right internal mammary , para vertebral node and omental deposit. After8 weeks of steroid-based therapy the patient underwent a second 18F-FDG PET/CT scan for response evaluation which showed regression in size and metabolic activity of above mentioned lesions. Discussion : Mainly IgG4 RD patients present with involvement of the pancreas, pancreatobiliary tract, lacrimal and salivary gland, lung, retroperitoneal region and kidney. Our patient presented with mixed findings of vascular wall involvement and extensive distribution of multiple lesions that could not be interpreted as common metastasis of malignancies. According to one cohort study strong indicator of IgG4 RD are 1) Diffusely elevated 18F-FDG uptake in organs, mainly involving salivary glands, pancreas, and prostate, 2) Patchy 18F-FDG-avid lesion without signs of infection, mainly involving aorta wall, retroperitoneal region, pancreas, bile duct, liver, kidney, and lung and 3) weak indicators are multi-organ involvement while 4) significant and rapid response to steroid-based treatment is also a strong indicator. Our patient showed clinical improvement with partial FDG PET-CT response to steroid therapy. Conclusion :Use of PET-CT in IgG4 RD is useful for intial assessment and response to treatment as well.
| Musculoskeletal Imaging|| |
Role of Three Phase Bone Scintigraphy and SPECT/CT in Varied Presentation of Osteoid Osteoma
D. Anitha, Shwetal Ghule Pawar, Suruchi Shetye,
G. H. Tilve
Department of Nuclear Medicine, Seth G.S Medical College and KEM Hospital, Mumbai, India
Background and Aim: The purpose of this study is to retrospectively evaluate the efficacy of three phase bone scintigraphy and SPECT/CT in diagnosing osteoid osteoma when the clinical features are misleading and conventional radiographs are equivocal or normal which occurs in varied locations of the lesions and evaluating radiofrequency ablation response for osteoid osteomas. Materials and Methods: Data of 17 patients (age range from 7-35 years) who had undergone Tc-MDP BS with SPECT/CT from 2011 till august 2015 was analysed. Of which data of 6 patients before and after radio frequency ablation and data of 11 patients (age range from 17-56 years) who had undergone Tc-MDP BS with SPECT/CT for clinically and/or radiographically suspected osteoid osteoma of vertebra (1 cervical,1dorsal,1 dorso lumbar and 1 lumbar); humerus (2 cases); forearm (2 cases); iliac (1 case); femoral (6 cases); tibia (2 cases); fibula (1 case) were retrospectively evaluated. BS images were analysed by an experienced nuclear medicine physician. CT images were evaluated by an experienced radiologist. SPECT/CT images were evaluated by the nuclear medicine physician. On the basis of the diagnostic confidence the interpreters used a scoring scale of 1-3, in which 1 is negative for osteoid osteoma, 2 is equivocal, and 3 is positive for osteoid osteoma. Results: Comparing the pre RFA scans and post RFA therapy bone scan (both planar and SPECT) imaging, it is evident that there is reduction in the tracer uptake corresponding to the reduction in the osteoblastic activity and correlates with the symptoms in all the patients (100%). CT/MRI findings were kept as standard in respective cases. All the cases in varied locations were diagnosed precisely. Conclusion: Planar BS and SPECT studies not only confirm osteoid osteoma and localize preciselythe osteoblastic activity of the clinically misleading and radiographically undiagnosed tumours but also are used for follow up of treatment response with RFA. CT findings cannot differentiate between treatment response that was evident on bone scan as early as 1 months. The varied locations of osteoid osteoma were also noted.
Coincidental Detection of Meningioma on F-18 NaF Whole body Bone Scan in a Patient with Carcinoma Cervix
RamyaPriya R *, Krishna Mohan V S*, Ranadheer Gupta M*, Manishi L. Narayan*, Lakshmi AY**, Pranabhandu Das ***, Tekchand Kalawat *.
*Department of Nuclear Medicine, **Department of Radiology and ***Department of Radiotherapy. Sri Venkateswara Institute of Medical Sciences, Tirupati - 517507, Andhra Pradesh, India
Background and Aim: Radionuclide Tc 99m methylene diphosphonate bone scintigraphyand fluorine -18 sodium fluoride positron based bone scan are routine tests for localization of focal abnormal sclerotic changes in skeleton. We are presenting a case of carcinoma of cervix, examined with F18 NaF bone scan to rule out skeletal metastasis. Incidentally, F 18 NaF, Bone scan detected an area of intracranial radiotracer uptake site, an interesting finding, not related to the primary malignancy. Case History: A 65 year old, female patient, known case of carcinoma of cervix, diagnosed and treated in 2013. Her primary tumor histopathology revealed non keratinizing, squamous cell carcinoma of cervix, for that she underwent trans-abdominal hysterectomy, bilateral salpingo oophorectomy and pelvic lymph node dissection and followed by local radiotherapy in November 2013. In April 2014, patient presented with back pain, with no other complaints related to primary disease diagnosed and treated earlier. On clinical, per vaginal and symptomatic local examination, no positive findings observed, considering the possibility of metastasis, routine investigations and radionuclide bone scintigraphy to rule out bone metastasis. F18-NaF whole body PET CT bone scan performed. Her scan findings revealed linear increased tracer concentration in L-5 vertebra, suggestive of post radiotherapy osteoporosis and insufficiency fracture, leading to back pain. In addition to this observation, bone scan highlighted an abnormal right side intracranial lesion. The incidentally detected lesion diagnosed as extra axial meningioma, when correlated with CT scan images of PET CT scan. She was further clinically evaluated for this coincidentally detected meningioma, and found with no obvious neurological deficit. Conclusion: F18 NaF bone scan is a hybrid imaging modality, have advantage over conventional bone scan in providing the functional and structural information. The morphological details helps in reading of the bone scan images with CT details, improves its specificity in interpreting osseous and non-osseous unusual lesions.
| Nephro Urology|| |
Decay corrected delayed image for better interpretation of dynamic renal scintigraphy equivocal for presence or absence of obstruction
Anand Kumar D, Kumaresan K
KK Nuclear Scans, Raj Bhavan Road, Somajiguda, Hyderabad, India
Background and Aim: Delayed static image is routinely obtained after dynamic Tc 99m DTPA/ EC renal scintigraphy when the study is equivocal for presence or absence of obstruction. Visual comparison of iso-time (1 min) delayed image with initial post dynamic (post void) static image is highly subjective and can be misleading in some cases.
Materials and Methods: We have performed decay correction of the delayed image and then made a comparison qualitatively and quantitatively with the post dynamic (post void image) using the software supplied for Gastric Emptying study. A study was carried out to assess the impact of this decay corrected image on the final interpretation.
Results: Total of 69 studies where one kidney had equivocal findings were included in the study. Based on conventional comparison of delayed image, drainage was reported in 9 cases (Group- I) and drainage could not be detected in 60 cases (Group- II). When decay corrected delayed image was compared with earlier post void image, the findings were as below:
Conclusion: When drainage could not be appreciated in dynamic scintigraphy, 'decay corrected delayed image' helps to identify drainage confidently in 48 % of the cases. This can be done easily by adopting the vendor supplied software for Gastric Emptying study.
Utility of Hilson's Perfusion Index in evaluation of Renal Allograft function-SVIMS Experience.
Mehabunnisa SK*, Amruta lakshmi R*, Ramyapriya R *,
Krishna Mohan V S*, Ranadheer Gupta M*, Manishi L. Narayan*,
Ram R**, Shiva Kumar V**, Tekchand Kalawat *
*Department of Nuclear Medicine, **Department of Nephrology. Sri Venkateswara Institute of Medical Sciences, Tirupati - 517507, Andhra Pradesh, India
Background: Delayed graft function is one of the commonest complications of renal transplantation. Dynamic renal scintigraphy scores above other methods for evaluating grafts as it is non-invasive, safe, fast, reproducible and able to demonstrate perfusion function and drainage pattern. One of the difficult clinical scenarios in evaluation of delayed graft function is to rule out rejection. Perfusion indices have an important role in the diagnosis and etiology of delayed graft function and ruling out rejection. Aim : To study the role of Hilson's perfusion index in the diagnosis of delayed graft function and ruling out rejection.
Materials and Methods : In this retrospective study, we have evaluated renal transplant recipients with renal scintigraphy within 7 days post transplantation, from January 2013 to July 2015. A total number of 20 patients were examined with technetium 99m DTPA renogram within 7 days post transplantation. Patient preparation and data acquisition performed as per the standard guidelines. The images were acquired at 1 second per frame for first 60 seconds and then 15 seconds per frame for 30 minutes. Time activity curves were obtained for 1 st minute images to evaluate the perfusion of graft and iliac arteries. Hilson's perfusion index is calculated as Arterial counts per cell integrated to peak x100/concurrent renal counts per cell. Results : In 17/20, perfusion index was less than 100 and the patients had only clinical and biochemical follow up. In 3/20 perfusion index was more than 100 but less than 150 and the patients had biopsy proven acute tubular necrosis. None of the patients had perfusion index more than 150. Hilson's perfusion index could differentiate acute rejection from acute tubular necrosis with high accuracy. Conclusion : Hilson's perfusion index with slight modifications of taking cortical region of interests into consideration and ruling out renal artery stenosis prior interpretation can non-invasively rule out rejection and help in diagnosis of delayed graft function.
Incidental Unusual Diagnosis on Renal Scans
Veerabhadra Radhakrishna 1 , Bibekanand Jindal 1 , Bikash Kumar Naredi 1 , Srinivas 2 , Dhanapathi Halanaik 2 .
Department of Paediatric Surgery 1 , Department of Nuclear Medicine 2 , JIPMER, Pondicherry, India
Background: Nuclear medicine is a very powerful tool in modern medicine with a wide diagnostic and therapeutic capability. There are reports in medical literature of nuclear imaging clinching a diagnosis, where otherwise it doesn't have primary role in the diagnosis of that condition. Herein we report three cases where renal scintigraphy played important role in initial diagnosis which benefitted the patient. Case History: Two of the cases presented with UTI, which was suspected to have duplex renal moiety on cortical scan (Ultrasonogram missed the diagnosis in both cases) and confirmed further with IVP and MRU, one of them underwent upper moiety heminephroureterectomy and the other uretero-ureterostomy. Both patients thriving well, follow up uneventful. The other case of UTI suspected to have pelvic mass on renal scintigraphy pushing the bladder antero-superiorly was further confirmed on CT scan, further evaluated to find Neuroblastoma, treated with surgery and chemotherapy. Patient is on follow up, no recurrence. Conclusion: Although incidental finding, duplex renal moiety can be diagnosed by renal cortical scan/renal scintigraphy. In addition it can give an unusual clue of presence of a mass in the pelvis or retroperitoneum when in scintigraphy we can see the displaced bladder or the kidney. However, further imaging in form of MRI or CT scan is needed depending on the condition suspected. We stress on the fact that it's important to look at all aspect of the image, to include those areas outside the region of interest, which may significantly benefit the patient.
| Nuclear Medicine Physics|| |
Evaluation of reconstruction algorithms to validate the NEMA phantoms results in clinical scenario - A comparative study using time of flight versus non-time of flight patients' PET data acquisition
Ankit Watts, Ajay Chitkara, Pearl Jacob, Baljinder Singh, Bhagwant Rai Mittal
Department of Nuclear Medicine & PET, PGIMER, Chandigarh
Background and Aim: The aim of the present study was to standardize the reconstruction parameters for TOF and Non-TOF PET data using NEMA IQ NU-2001 body phantom & validate the phantom results in patients. Materials and Methods: In this study 3-dimensional acquisitions were done on two different prototypes PET scanner (LYSO based TOF & BGO based Non-TOF). NEMA IQ NU-2001 body phantom was filled with 55MBq activity of 18 F-FDG to provide spheres: background radioactivity ratio of 4:1. Phantom data was acquired uniformly (single bed position/2 min acquisition) using different prototype PET scanners (TOF LYSO , NON-TOF LYSO , NON-TOF BGO ). PET data acquired on NON-TOF (LYSO and BGO crystals) and TOF (LYSO crystal) was reconstructed using ordered-subsets expectation maximization (OSEM) algorithm. For achieving the best image results, the number of iterations and subsets of data reconstruction were varied. 18 F-FDG PET data acquired by using a standard Institute protocol in forty-six (10 patients on NON-TOF BGO , 30 on TOF LYSO , 6 on both TOF LYSO , & NON-TOF LYSO -52 PET acquisitions in total) lymphoma patients were also analyzed by varying the reconstruction algorithms as described for phantom data. Qualitative and quantitative assessment was done by visual scoring method and by computing SNR, contrast & noise values respectively. Results: On visual scan interpretation, the best quality phantom images on TOF LYSO & Non-TOF BGO and Non-TOF LYSO were seen on 2 nd and 3 rd iterations respectively. Likewise, the results of clinical data were in consonance with the phantom data. The quantitative analysis using SNR values for smallest 10mm sphere were found to be highest for TOF LYSO (20.66 at 2 nd iteration) followed by NON-TOF LYSO (10.80 at 3 rd iteration) & least for NON-TOF BGO (8.48 at 2 nd iteration). Similarly, trade off between Contrast & noise values were found to be best for TOF LYSO followed by NON-TOF LYSO & least for NON-TOF BGO in all the set of iterations for both phantom & patient data. PET data acquired in 6 patients both in TOF and Non-TOF modes demonstrated that the former provided better image contrast and definition of the smallest lesions (lymph nodes) both on visual scan interpretation and quantitative analysis. Conclusion: NEMA phantom (IQ NU-2001) derived reconstruction parameters can be used confidently in PET scan acquisition in clinical scenario. Undoubtedly, TOF based PET technology provides better overall image contrast, definition and resolution for the smaller (~10 mm) lesions.
Dosimeteric Comparison of 90 Y-SIRSphere and 90 Y-TheraSphere therapy
Ashish Kumar Jha 1 , Sneha Mithun 1 , Nilendu C. Purandare 1 , Sneha Shah 1 , Archi Agrawal 1 , Suyash S. Kulkarni 2 , Nitin Shetty 2 , Venkatesh Rangarajan 1
1 Department of Nuclear Medicine and Molecular Imaging, 2 Department of Raiodiagnosis, Tata Memorial Hospital, Parel, Mumbai - 400 012, India
Background: Inoperable primary and secondary hepatic malignant tumors are conventionally treated by local intervention like external beam radio therapy (EBRT), trans-arterial chemoembolization (TACE) or radiofrequency ablation (RFA). The limitation of EBRT in the treatment of primary or metastatic liver tumor is to deliver lethal dose to the tumor within the tolerance limit of normal liver parenchyma to radiation. The lethal radiation dose required to kill the malignant liver tumor is estimated to be more than 70Gy. But the dose delivered to the tumor by EBRT under the liver tolerance dose is less than 35Gy in 1.8Gy/day fractions, which is much lower than the required lethal dose. Transarterial radioembolization (TARE) is capable of delivering higher than the lethal dose. Two food and drug authority (FDA, USA), approved commercial 90 Y-microsphere products are available in the market. 90 Y-TheraSphere, MDS Nordion, Ottawa, Ontario, Canada (Biocompatibles UK Ltd, Surrey GU9 8QL, UK) and 90 Y-SIRSpheres, Sirtex Medical Inc, Sydney, Australia. TheraSphere is 90 Y-Glass-Sphere which measures between 20 to 30µ in diameter and is tagged with 90 Y. Specific activity of 90 Y-Theraspher is as high as 2400-2700 Bq/Sphere. 90 Y-SIRSphere is 90 Y resin microspheres which are the polymer beads having diameter between 20 to 40µ. Specific activity of 90 Y-SIRSphereis very low around 40-70Bq/Sphere. Aim of our study is to compare the radiation dose delivered to the tumour by these two commercially available microspheres. Material and Method: Total 86 patients' data, 46 treated by 90 Y-TheraSphere and 42 treated by 90 Y-SIRSphere were utilized to draw the comparison between these two microspheres. Planned dose of 90 Y-TheraSphere administered was considered as the radiation dose delivered and for 90 Y-SIRSphere radiation dose delivered was calculated from the activity administered. Radiation dose delivered by two microspheres were compared by using statistical tests. Result: In our study we found that the average radiation dose delivered to the tumor by 90 Y-TheraSphere and 90 Y-SIRSphere are 124Gy and 53Gy respectively. Dose delivered by 90 Y-TheraSphere is significantly higher (p value=0.000) [Table 1]. Conclusion: Our study suggests that the radiation dose delivered to the tumor by 90 Y-SIRSphere is lesser than the lethal dose required.
Contrast in the CT slice image corresponding to liver of whole body PET/CT scan can be enhanced using imadjust function available in the MATLAB
Deepak Aheer, AK Pandey, Chetan Patel, CS Bal,
Department of Nuclear Medicine, All India Institute of Medical Sciences, New Delhi, India
Background and Aim: Tissue Contrast depends on the energy of x-ray beam, effective atomic number and density of the tissue under examination. Since all these three parameters remains constant in case of liver, therefore, liver on CT scan appears homogenous. HCC tumours are highly vascular in nature. Small density difference between tumour cells and hepatocytes results in poor contrast between the two. Whole body PET/CT scan is performed without using contrast while in diagnostic CT, dual phase contrast examinations are performed in case of patients having suspected HCC tumours. This study was conducted to improve the contrast between the HCC tumours and hepatocytes using contrast enhancement functions available in MATLAB for CT images acquired as a part of whole body PET/CT examination. Material and Methods : CT slice image (corresponding to liver) one for each of the fifty patients who underwent whole body PET/CT for the evaluation of suspected HCC tumour, were exported in jpeg format. These scans were acquired on Siemens Biograph mCT with 120 KVp with CareDose ON. A Matlab script was written to read and process these images for constrast enhancement. First of all Median filter was applied that smooths the image while retaining the edge information, and then constrast of the image was enhanced using the three matlab functions namely histeq, adapthisteq , imadjust, . Finally,the image quality was assessed by using universal image quality index. Result : Table-1 lists the average, standard deviation, maximum and minimum value of image quality index. From the table it is clear that the imadjust outperforms all among the three techniques used for contrast enhancement. A representative image is shown in figure-1. Conclusion : Contrast in the CT slice image corresponding to liver can be enhanced using imadjust function available in the MATLAB.
Respiratory Motion Correction Using Non-Rigid Registration Method with PET Specific Constraints in PET/Ct Acquisitions, Jaslok Hospital: An Initial Experience
Laxman Khande, Tattwamasi Bharadwaj, Hina Shah, P Saisradha, Hemant Rathore, Prasenjit Chaudhuri, Vikram R Lele
Jaslok Hospital and Research Centre, Mumbai, India
Background: Respiratory motion induces motion related artifacts causing image distortion and potentially leading to apparent increase in lesion size, reduction in standard uptake value and potentially missing small lesions. Conventional techniques- Deep inspiration breath hold technique, quiescent period gating and 4 D phased matched PET CT (motion match) have numerous limitations. Qfreeze a global non-rigid registration technique withPET specific constraints with proposed better estimation of size, SUV potential detectability of small lesions. We portray our initial experience in Respiratory Gating of PET using this method and comparing it with conventional non gated PET images quantitatively and qualitatively. Materials and Methods: 5 patients having lesions near the liver-diaphragm interface region and small lung nodules with marginal uptake were randomly selected for respiratory gating. Patients with respiratory distress, poor general condition and of pediatric age group were excluded. Patients were instructed regarding breathing maneuvers and dummy exercises were performed. ANZAI belt device was harnessed to the abdomen and calibrated for breathing pattern of the patient. Gated PET images were acquired at each phase of respiration and data binned in list mode to respective 6 phases of respiration. PET specific constraints like 3D image estimation through optical flow vectors, regularization through tissue viscosity and tissue elasticity algorithms, application of statistical median algorithm, matrix convergence through multiresolution and rebinning to 100% through statistical median algorithm thus, achieved to integrate it into 3D pet image. Which was analysed and reported. Results: Visual assessment showed improvement in sharpness, better registration of lungs and liver lesions and finding new lesions by respiratory gated PET-CT images over the conventional images. Quantitative assessment revealed 8.32%(+/-0.125%) mean increase in SUVmax and 30.10%(+/-0.148%) decrease in volume in gated images as compared to non-gated images. Conclusion: This pilot study strongly supports the evident superiority of Gated images over non Gated images both quantitatively and qualitatively highlighting its importance. Thus, we recommend its appropriate use in patients with lung and liver lesions in and around the liver diaphragm interface and in small lung nodules with marginal uptake. However appropriate breathing, time constraints and patients with Respiratory distress, poor general condition and belonging to paediatric age group still pose a challenge in its efficient utilization.
Correlation of Initial Dose Rate, Cumulative Absorbed Dose, Remnant Size with Ablation of Thyroid Remnant In Children And Young Adults Undergoing Radioiodine Therapy
Praveen Kumar*, Nishikant A Damle, C.S. Bal
Department of Nuclear Medicine, All India Institute of Medical Sciences, New Delhi
Background and Aim: The recommended cumulative absorbed dose for successful ablation of thyroid remnants is ≥300 Gy and the initial dose rate should be ≥0.6 Gy/hr. The dose rate delivered in the first 24-48 hours is important to achieve complete ablation. The aim of this study was to calculate the initial dose rate (Gy/hr), cumulative absorbed dose (Gy) and size of lesion (gm) and correlate these parameters with success of ablation in children and young adults. Materials and Methods: Twelve patients (M=5, F=7; PCT=11, FCT=1) with age ≤21 years with thyroid remnant only or remnant with nodes and/or metastasis were given empiric therapy dose of radioiodine. Seven patients had remnant only, 4 patients had remnant and nodes while 1 patient had remnant, nodes and bilateral diffuse lung metastases. The initial dose rate to lesions was analyzed using the formula (ICRP Publication 38):
D (Gy/hr) = 0.58 x 0.19C = 0.11C
where, C (MBq/gm) is the concentration of activity in lesion while Absorbed dose in lesion was calculated based on Maxon approach:
Dose (cGy) = 0.63 x C 0 x T 1/2eff lesion
where, C 0 (µCi/gm) is the initial radionuclide concentration in the lesion and T 1/2eff (hr) is the effective half life of 131 I in the lesion. Results: The median and range of empiric activity, mass, initial dose rate and cumulative absorbed dose were found to be 37.5(30-102) mCi, 0.8(0.08-6.33) gm, 1.77(0.73-16.51) Gy/hr and 199(58-1263) Gy respectively. In 12 patients there were 15 thyroid remnants. 5/5 remnants that received ≥300 Gy and 9/10 remnants that received <300 Gy were completely ablated. All remnants received initial dose rate of >0.6 Gy/hr whereas only 3/15 remnants received >3 Gy/hr. The non-ablated remnant received 1.71 Gy/hr, cumulative absorbed dose of 262 Gy and size of remnant was higher i.e. 6.33 gm. One patient who received initial dose rate of 0.71 Gy/hr and another patient who received 58.2 Gy of cumulative dose were also completely ablated with a single dose of radioiodine. Conclusion: This study, although limited by sample size, shows that remnants can be ablated even at cumulative absorbed doses less than 300Gy with dose rates of ≥ 0.6 Gy/hr. However, failure may be seen in a large size of remnant. This is especially significant in children, where the aim of radioiodine therapy is to achieve ablation with minimum possible radiation dose.
Oasis IRiS3D: Fast OSEM3D SPECT Reconstruction with GPU
8310 Guilford Rd, Columbia, MD 21046, United States
Background and Aim: OSEM3D is generally admitted as an efficient reconstruction method for SPECT Imaging, but may be time consuming when calculations are performed on central processor unit (CPU). To speed up reconstruction we have implemented an OSEM3D application in Oasis, namely IRiS3D using the graphic processing unit (GPU). GPUs are dedicated graphics rendering devices used by all computer graphic cards. The parallel nature of the graphics pipeline is particularly adapted to the reconstruction problem. Materials and Methods: Segami's IRiS3D, an OSEM3D reconstruction implementation is programmed on GPU. The projection and backprojection operators of OSEM3D include collimator with detector varying response model. Optionally, tissue attenuation is considered during the iterative process (OSEM3D+AC). Images are loaded on graphic cards as texture with the OpenGL library and computations are carried out using arithmetic operations of fragment shaders. Two internal data representations were tested: 16 bit and 32 bit floating point data. No pre-computed matrix coefficients are needed for GPU method. Our OSEM3D implementation was tested on simulated data and was compared with a classical CPU implementation. Projections were calculated taking into account the spatially varying resolution due to the collimator response, attenuation and statistical noise. Although IRiS3D application includes scatter correction, the data represented here does not use the scatter correction. To evaluate our method we computed the Euclidean distance between the known reference object and the reconstruction and we plot this against the number of iterations. Additionally, for clinical validation we reconstructed patient data from brain and cardiac images. Reconstruction times were measured on a standard PC (Dell XPS, GPU: GeForce 7950GX2, CPU: Intel Core 2 Duo E6700 2.66GHz) for 128x128 120 projections brain images. Results: The use of 16 bits precision instead of 32 bits has a negligible effect on image quality, and is ten times faster. So it is clearly not indicated to go until the highest precision. In 16-bit programming, we performed 8 iterations with 5 subsets of OSEM3D in 30 seconds and OSEM3D+AC in 107 seconds on GPU instead of about 1 hour and 10 hours, on CPU respectively. With continued advances in GPU libraries and improved video cards, the reconstruction time continues to decrease. Conclusion: Segami's IRiS3D, an OSEM3D with GPU implementation, provides a real gain of time and allows the use of this algorithm in a clinical context and on a standard PC.
| Oncology|| |
Efficacy of Tc99m-MDP and Tc99m-MIBI in Detecting Malignant Tissue in the Breast
B. K. Das 1 , P. K. Pradhan 2 , Sudatta Ray 1
1 Utkal Institute of Medical Sciences, Bhubaneswar, 2 S.G. Postgraduate Institute of Medical Sciences, Lucknow, India
Background and Aim : Most breast cancer patients come in stage II and above, many times delayed due to absence of a definitive diagnostic procedure. X-ray mammography and other imaging modalities lack in specificity in comparison to scintimammography (SMG) which is performed using Sestamibi or Tetrofosmin. Efforts have been made to use MDP in place of Sestamibi which is significantly cheaper and has also the advantage of obtaining bone scan on the same day in one go.. The purpose of this study is to compare the efficacy of both agents. Materials and Methods: 123 consecutive patients with confirmed diagnosis of breast cancer were subjected to scintimammography using 20 mCi of Tc99m-MDP (BRIT, BARC,Mumbai) and a dual headed gamma camera using standard technique. Scintimammography was performed in another 105 consecutive similar patients using the same standard technique and equipment but with Tc99m-Sestamibi (Sanlar). 30 patients clinically suspected of having breast cancer and later confirmed were subjected to SMG using both agents on two separate days. Each scan was evaluated by two nuclear physicians.Ratio of tracer uptake in the lesion and normal tissue was calculated. Results: Sensitivity and specificity was found to be 96.9 % and 92.2 % respectively in patients performed with Tc99m-MDP and 98.1 % and 93.7 % respectively in patients using Tc99m-Sestamibi. Out of 30 cases in whom SMG was performed using both agents, 28 (93 %) showed concordant findings (both positive 16, both negative 12 ). In two patients Sestamibi scans were positive but MDP scans were negative. In 16 MIBI positive cases 3 showed concentration in axillary lymph nodes which was not seen in MDP scan. In 16 MDP positive cases 4 showed metastatic involvement of the skeletal system. The activity ratio in MIBI and MDP scans were similar and varied from 1.3 to 5.7. In one case a small lesion in the other breast was not visualized in MDP scan. Conclusions: The sensitivity and specificity found in our studies is higher than in many published multi-centric studies which may be due to the fact that most patients were in stage II and higher at the time of diagnosis.Tc99m-Sestamibi is potentially better than Tc99m-MDP in detection of malignant lesions. However, MDP is not only cheaper, but the whole body bone scan which can be performed in one go can provide vital information regarding metastatic involvement of the skeletal system. Tc99m Sestamibi remains the choice radiopharmaceutical for early diagnosis of breast cancer. However, Tc99m-MDP can be recommended for diagnosis of breast cancer in cases suspected to be in stage II and higher with the additional benefit of getting vital information regarding involvement of skeletal system.
Detection of unknown primary from various metastatic sites by PET-CT
Prashanth A, Barai S, Gambhir S, Sankar G, Singh A, Yadav N
1 Department of Nuclear Medicine, Sanjay Gandhi Post Graduate Institute of Medical Sciences, Lucknow, India
Background and Aim : PET-CT has proven as a useful modality for diagnosis of unknown primary lesions (CUP).The results vary widely. In this study we try to find the percentage of malignancies detected reliably by PET-CT. Materials and Methods: Retrospective study was performed by analyzing the PET-CT scans done for detection of CUP. Patients were included if there was a known metastatic disease with unknown tissue of origin and conventional imaging could not delineate the probable site of origin. A total of 81 patients were studied and classified according to metastatic site peripheral lymph nodes,(PLN) n=23, bone n=24, brain n=12, liver n=6,peritoneum n=4 and , others n=12. Results: When the proportion of positive PET-CT scans is compared to metastatic sites we found a wide variation. It ranges from 71% (17/24) for bone metastasis, 43% (10/23) for PLN (cervical, axillary, mediastinal abdominal and inguinal), 67% (8/12) for brain, 67% (4/6) for liver, 25% (1/4) for peritoneum, and 25% (4/12) for other sites. Sub analysis for cervical lymph nodal disease reveals primary in 50% (10/20) of cases. Conclusions: The success rate for identification of CUP depends on the location of metastatic disease. When patients present with cervical nodal metastasis or malignant ascites poor performance of PET-CT is expected whereas it has excellent detection rate for bone metastatic disease.
Diagnostic Utility of 18 F FDG PET/CT in Patients of Differentiated Thyroid Carcinoma with Elevated Thyroglobulin and Implication on Management - An Institutional Experience
Manjit Sarma, Padma S, Shanmuga Sundaram P
Department of Nuclear Medicine and Pet Ct, Amrita Institute of Medical Sciences And Research Centre, Cochin, Kerala, India
Background and Aim: Negative whole body iodine scans with elevated thyroglobulin (TENIS) on follow up in patients treated with high dose 131 iodine for differentiated thyroid carcinoma is frequently encountered. Another closely related subgroup of patients is in whom there is disproportionately increased thyroglobulin with minimal disease detected on followup 131 iodine whole body scans. 18 F FDG PET CT is being increasingly used for evaluation of TENIS patients for detection of dedifferentiated disease and may also have a role in delineating the disease burden in the other subgroup.We aimed to evaluate the diagnostic utility of FDG PET CT in our population with TENIS and also its role in delineating the disease burden in patients in whom there is disproportionately increased thyroglobulin with minimal disease detected on followup 131 iodine whole body scans. Material and Methods: Study included 52 patients of DTC post 131 iodine treatment on follow up (male: female=11:28, age range=23-59 years, range of Tg =14.8-3885 ng/ml). Out of the 52 patients, 45 patients (Group A) had negative whole body 131 iodine scans with elevated thyroglobulin (TENIS) while 7 patients (Group B) had disproportionately increased thyroglobulin with minimal disease detected on followup 131 iodine whole body scans. A standard protocol for whole body FDG PET with non contrast enhanced CT was followed. 18 F FDG PET CT findings, FNAC /USG guided FNAC or biopsies of suggested metastatic sites (when applicable) and findings of 131 iodine scans showing minimal disease were correlated. Results: In group A (45 patients), FDG PET CT detected FDG avid lesions (thyroid bed lesions/lymphnodes /distant skeletal metastases) in 23/45 (51%). In patients who had Tg values less than 50 ng/ml (8/45 patients) FDG avid disease was detected in thyroid bed/cervical nodes or in lungs (above diagphragm lesions). In group B patients (7 patients), additional lesions (FDG avid) were detected in 4 patients (4/7 patients). Conclusion: 18F-FDG PET CT is an useful modality for detecting dedifferentiated lesions in patients with TENIS. In TENIS patients with Tg values less than 50 ng/ml, a regional FDG PET CT may suffice which may have economic as well as radiation exposure implications. In patients with disproportionately increased thyroglobulin with minimal disease detected on followup 131 iodine whole body scans , 18 F FDG PET CT may be useful in detecting additional dedifferentiated lesions (disease burden estimation).
Clinical utility of 18 F-FDG PET/CT scan in primary bone tumour
Ram Singh Meena, Rahul Parghane, Ashwini Sood, Anish Bhattacharya, Bhagwant. Rai Mittal
Department of Nuclear Medicine, PGIMER, Chandigarh, India
Background and Aim: Imaging plays an important role in the evaluation of primary bone tumors. Aim of this study was to evaluate the role of 18 F-FDG PET/CT in staging, restaging, recurrence detection and changes in management of primary bone tumor patients. Material and Methods: Clinical records of patients with bone tumor, who had undergone 18 F FDG PET/CT scan from April 2014 to August 2015, were reviewed retrospectively. Patients were also subjected to CT, MRI for characterization of lesion and to look for metastatic disease. The final diagnosis of primary bone tumor was confirmed by histopathological examination after biopsy or surgical excision of the lesion. 18 F-FDG PET/CT scan was performed using standard protocol. PET scan finding were divided into four categories - site of primary bone tumor, other skeletal sites, lung lesion and regional lymphadenopathy. The lesion detected on PET scan was verified by tissue diagnosis after surgical excision and follow up PET scan, further imaging and follow-up. Results: A total 33 diagnosed cases of primary bone tumor (19 male, 14 female; mean age 28 years, range 10-60 years) were analyzed retrospectively. Of the 33 patients, 12 were diagnosed to have osteosarcoma, 9 Ewing's sarcoma, 3 giant cell tumor, 8 chondrosarcoma and 1 enchondroma. PET/CT was used for initial staging in 7 patients, restaging/ response evalution in 7 patients, recurrence detection in 8 patients and surveillance in 11 patients. In staging of primary bone tumor, PET scan showed abnormal FDG uptake at primary site in all the 7 patients, lung lesions in 4 patients. Three of these 7 patients (42%) received additional therapy based on PET findings. In restaging/response evaluation, PET showed abnormal FDG uptake in other skeletal site in 2 patients, lung lesions in 3 patients. Two of the 7 (28%) patients in this category received additional chemotherapy and surgical excision in 1 patient (14%). Of the 8 patients evaluated for recurrence, PET scan was positive for recurrence in 2 patients (25%). PET scan show abnormal FDG uptake in other than primary skeletal site in 1of the 11 patients studied for surveillance. Four patients (36%) received chemotherapy and surgical excision in 1 patient (10%). Conclusions: Our result show that whole body 18 F- FDG PET/CT scans is very useful in detecting lesions at other site in addition to primary skeletal lesion and helps in deciding additional therapy based on PET scan findings.
Evaluation of the role of 99mTc-MDP bone scan for follow-up and assessment of the treatment response in metastatic breast cancer
Soumendranath Ray, Jayanta Das,
Tata Medical Center, Newtown, Rajarhat, Kolkata - 700 156, India
Background and Aim : Bone metastasis is common in breast cancer. The aim of this study was to re-evaluate the role of 99mTc-MDP bone scan for follow-up and assessment of the treatment response in metastatic breast cancer. Materials and Methods: Radionuclide bone scan of 537 female breast cancer patients were performed in our department from September 2011 to august 2013. The results of these baseline scans were correlated with T stages of the disease. Follow-up bone scans of 120 patients were performed. The data was retrospectively analyzed. While analyzing the results of follow-up scans, identification of new lesions and extent and severity of the existing lesions were taken into consideration to evaluate treatment response. Results : Out of 537 patients who underwent the baseline bone scan, one had carcinoma in situ, 23 of them had T1 lesion, 158 ladies had T2, 101 women had T3 and 158 ladies had T4 lesions .T staging was not known in 96 patients. Bone metastases were detected in 96 patients and bone scan was normal in rest 441 ladies.More than 75 % patients who had a positive bone scan were asymptomatic Incidence of positive scans was higher in locally advanced disease (35% in patients with T3 & T4 lesions against 23% for combined CIS,T1,T2 lesions). Multiple metastases was noticed in 72 patients and 24 patients had solitary lesion. Vertebrae were found to be the commonest site of metastases(76 out of 374 total bone lesions).50 out of 96 patients had follow-up bone scan . Stable disease was noticed in 16 patients(32%). Disease progressed in 24 patients (48%)and there was partial interval treatment response in 10(20%). patients.75 out of 441 patients who had an initially normal bone scan underwent a follow-up bone scan.16 out of 75(21.33%) patients had metastases in the follow-up scan---7 of them had solitary lesion and 9 women had multiple metastases. Conclusion : In this study the importance of 99mTc-MDP bone scan for follow-up and assessment of the treatment response in metastatic breast cancer has been reiterated. This is a simple and robust technique which can objectively evaluate the response to treatment and also for follow-up of patients with an initially normal baseline scan.
Impact Of Acquisition Time On Image Quality and Quantification of F-18 FDG PET/CT Images
Jephy Joseph, Ajith Shinto, K. K. Kamaleshwaran, Radhakrishnan ER, Indira V. Upadya,
Department of Nuclear Medicine and PET, KMCH, Coimbatore-14, Tamil Nadu, India
Background and Aim : The purpose of this study was to evaluate the impact of acquisition time on image quality,lesion detection rate and standardized uptake value of F 18 FDG PET images in cancer patients.
Materials and Methods : 32 cancer patients over the period of 20 months were included in this study, 67 lesions were evaluated, two consecutive whole body F 18 FDG PET/CT scans using a 3 min and 1.5 min acquisition time per bed position were obtained for each patient. Lesions were visually identified and their locations were compared. SUV values of the primary tumor, lymph nodes and metastasis were determined and compared. Image quality was visually analyzed and quantfied in terms of lesion to background ratio(L/B) , scored on a 5 point likert type scale. For all parameters interobserver agreement was assessed. Results : All relevant lesions could be identified at both acquisition times. Image quality is slightly poor in 1.5 min than 3 min. but the quality of lesion visualization was excellent regardless of the acquisition time. SUV values of the images correlated well. Conclusion : Although image quality is slightly poorer, reducing acquisition time to 1.5 min per bed position seems to be clinically feasible without decreasing the lesion detection rate and quality of lesion visualization even for less experienced observers.
Pictorial Essay on Cold Vertebra in FDG PET-CT
Nikhil Seniaray, Harshul Sharma, Arpana Arbind, Abhinav Jaimini, Maria M D D'souza, Sanjeev Saw, Santosh Pandey, Dinesh Kumar, Rajnish Sharma, Anupam Mondal
Institute of Nuclear Medicine and Allied Sciences, Brig. S. K. Mazumdar Road, Delhi - 110 054, India
Background and Aim: A photon deficient ("Cold") vertebra on 18F-FDG PET is a known entity and can arise as a result of varying etiologies. A proper interpretation of this observation is required to make an accurate diagnosis for appropriate management. Materials and Methods: 21 cases with "cold" vertebrae on 18F-FDG PET/CT were selected and analyzed from a population of 400 patients with known malignancy who underwent whole-body 18F-FDG PET/CT for staging, disease viability assessment, response to treatment or suspected recurrence purposes. The patterns were studied and correlated with clinical history and the low dose CT done with the PET scan for attenuation correction and anatomical localization. Results: The most common cause for cold vertebrae was found to be post external radiotherapy, causing photopenia involving multiple vertebrae corresponding to the radiotherapy portals. Two other causes found in the study were the destruction of the vertebral marrow cavity by metastatic tumor cells and vertebral hemangioma. Characteristic features of "cold" vertebrae are described in the study with illustrations. Conclusion: Pattern recognition coupled with clinical history and CT correlation of "cold" vertebrae on 18F-FDG PET/CT can help in diagnosing correct underlying etiology which can help in better management of the patients.
"Cold PSMA" a potential radioprotector for salivary glands and tear glands in patients receiving 177 Lu- DKFZ-PSMA-617 radioligand therapy, a correlation of labeling efficiency with post therapy scan findings: An initial experience in Jaslok Hospital
Prasenjit Chaudhuri, Tattwamasi Bharadwaj, Hemant Rathore, Chanchala Kale, Anil Parab, Vikram R Lele
Department of Nuclear Medicine, Jaslok Hospital, Mumbai
Background and Aim: PSMA-617, is a ligand of Prostate-specific membrane antigen (PSMA), which is a surface protein on healthy prostate cells, but is found at higher levels on prostate cancer cells. PSMA is an ideal target, for diagnostic purposes as well as targeted therapies against prostate cancer. PSMA I&T can be chelated to 68 Ga for diagnosis and 177 Lu for therapy. Here initial experience of labelling PSMA-617 with Lutetium-177 and serendipitous observation of "cold PSMA" being a potential dose reducer to salivary and tear glands is described. Materials and Methods: LuCl 3 of specific activity of 25-30 mCi/microgram obtained from Perkin Elmer Ltd.DKFZ-PSMA-617 is obtained from DKFZ, Germany. Sodium ascorbate buffer (pH 4.5) prepared beforehand. In a sterile vial, 900 microlitre buffer added to 100 microliter of DKFZ-PSMA-617, pH checked. 200millicurrie of Lu-chloride added, vial sealed and heated in water bath at 90 degrees for 15 minutes. After the radiolabelling was completed, the labeled product was filtered through C18 Sep-pak catridge through 50% ethanol, then through 22nm sterile filter. 20 ml by adding NaCl. Diluted drop on Whatman QC strips and SG ITLC strips. Solvent for QC 50 percent acetonitrile and sodium citrate 0.1N. RF value between 7 and 8, and for ITLC was 0. Labeling efficiency 89-97%. 175-200 mCi of Lu-177-DKFZ-PSMA-617 was administered. Following therapy, whole-body planar scan on dual head GE Discovery 670 NM/CT. ROI drawn on Salivary glands and tear glands and salivary gland and tear gland to thigh was calculated. Results: We found that the pre-therapy values of labelling efficiency correlated very well with the post-therapy salivary gland and tear gland to thigh ratios and labelling efficiency (96%- 3.48, 92%- 3.07, 97%-4.41, 89%-2.96, 98%-4.41). Thus, showing low labelling efficiency correlating well with low salivary gland efficiency and thus highlighting the potential use of "cold PSMA" as a dose reducer for salivary and tear gland. Conclusion: Radiolabelling of DKFZ-PSMA-617 with Lu-177 correlates well with salivary and tear gland to thigh ratios on post therapy scan. And patients with low labellling efficiency showed lower salivary and tear gland uptake thus highlighting the use of "cold PSMA" as a potential dose reduction method.
Role of 18 F-FDG PET/CT in restaging of patients with primitive neuroectodermal tumor
Sameer Taywade, Rakesh Kumar, Nishikant Damle, Madhavi Tripathi, Chandrasekhar Bal
Department of Nuclear Medicine, All India Institute of Medical Sciences, New Delhi, India
Background: Primitive neuroectodermal tumor (PNET) is a rare malignant tumor arising from neuroectoderm with incidence of 4% of all soft tissue tumors. It is considered as a part of a spectrum of Ewing sarcoma family of tumors (ESFT), which also includes extraosseous Ewing's sarcoma, malignant small-cell tumor of the thoracopulmonary region (Askin's tumor) and atypical Ewing's sarcoma. Role of PET/CT has been studied in ESFT, however very few studies have elicited role of 18 F-FDG PET/CT in PNET. The aim of the present study was to evaluate the role of 18 F-FDG PET/CT in restaging of patients with PNET after surgery, chemotherapy or radiotherapy (RT). Material and Methods: A total 45 patients of PNET previously treated with surgery, chemotherapy or RT who underwent 18 F-FDG PET-CT were analysed retrospectively. Seventy five 18 F-FDG PET/CT studies were conducted on these patients. Out of these 45 patients, 28 patients underwent 18 F-FDG PET/CT once, 8 patients underwent twice, 6 patients thrice, 2 patients four times and 1 patient underwent this study five times. Mean age of patients was 18 years (range 3- 42 years). 18 F-FDG PET/CT study was evaluated by two nuclear medicine physician. Final diagnosis was made based on correlation with clinical, biopsy, follow up and other imaging modality. Result: Of 45 patients, 29 patients showed residual/metastatic disease on 18 F-FDG PET-CT. Sites of disease involvement apart from primary site were multiple skeletal sites (27%), lungs (15%), lymph nodes (11%) and bone marrow (7 %). Active disease involving more than one system was detected in 11 patients (24%). Two patients (4 %) with suspicious residual active disease on 18 F-FDG PET/CT were found normal on correlation with MRI and on follow up. Of 45 patients, 6 patients with normal 18 F-FDG PET/CT showed evidence of disease based on correlation with clinical or other imaging modality and on follow up. The overall sensitivity, specificity, PPV, NPV of 18 F-FDG PET/CT to detect active disease was 80%, 92%, 95% and 75 % respectively. Conclusion: 18 F-FDG PET/CT can evaluate the local and metastatic sites in patients with PNET and could be a valuable modality to assess the post treatment disease status in these patients.
| Radiation Safety|| |
Assessment of radiation exposure to students from bone scintigraphic patients to nuclear medicine students participating in performing scintigraphy
Chippy B, Raghi PJ, Vasumathi, Sumeet M, Rajesh K, Sibi O
Department of Nuclear Medicine, School of Allied Health Science, Manipal University, Manipal - 576 104, Karnataka
Background and Aim: To assess the radiation exposure to the nuclear medicine students participating in performing bone Scintigraphy.Practical knowledge of radiation exposure from bone scan patients is important for taking appropriate precautions against unnecessary radiation exposure for students who participate in performing the procedures. Materials and Method: Exposure to the nuclear medicine student who prepared the radiopharmaceutical, injected and acquired whole body bone scintigraphy of adult patients under the supervision of the guide at KMC Manipal was measured using PSDM 221 Pocket Dosimeter. Pocket dosimeter calibration was done just before the start of the study. The readings were tabulated and average exposure rate was calculated seperately for preparation and injection and for acquisition. Overall exposure rate was also calculated. Result: In this study we found that the radiation exposure to nuclear medicine students who perform the procedure (including radiopharmaceutical preparation, injection & acquisition) from a single bone scintigraphic patient is on an average 0.4 mR/ hr (0.00373 mSv) . During the preparation and injection phase, the student got an exposure of on an average 0.255mR (0.0023 mSv) from single patient and 0.174m R (0.001626mSv) during acquisition phase. Conclusion: In a nuclear medicine facility students can perform maximum 6 to 8 bone scan patients per day(only bone patients). The result of this study helps in determining the rotation time of students in bone scintigraphic procedure.
Monitoring of Patients after High Dose Radioiodine Therapy in DTC: To Assess the Impact of enhanced Radiation Level Discharge Limits from Isolation Ward Currently Enforce by Regulatory Authority (AERB) Govt. of India
Dhananjay Kumar Singh, Satyawati Deswal, Gaurav Kumar Sinha, A. Malhotra
Department of Nuclear Medicine, Dr. Ram Manohar Lohia Institute of Medical Sciences, Lucknow, India
Background and Aim: The objective of this study was to compare the duration of stay of patients in Hospital under current and old criteria of discharge limits fixed by AERB, Govt. of India, Mumbai and assess the throughput of patient with revised criteria (AERB Safety Code: AERB/RF-MED/SC-2 (Rev. 2) , Nuclear Medicine Facilities, 2011) for discharge of patients from Isolation ward. Also simultaneously we tried to evaluate and find the radiation level at different distances from the patient immediately and at regular interval till they released from hospital after oral administration of therapeutic activity of Iodine-131 from the abdomen level with the help of calibrated radiation survey meter.
Materials and Methods: We retrospectively analyzed the external exposure rate in Sixty (60) cases. Thyroid monitoring for radioiodine is one of the best examples that directly determine the quantity of a radioactivity in an organ / body. A relation exists between the amount of activity administered and the dose rate at a given distance from the patient. However dose rate also depends upon the body built of the patient. The dose rate will be more for a given administered activity for thin patients than obese patients due to attenuation by abdominal wall. The safety guideline are however same for these patients. Results and Conclusion: After enforcement of current enhanced radiation level discharge limits of Isolation ward patient throughput has increased and we can simply admit more no. of patients in Isolation ward for High Dose Radioiodine therapy. However in few patients with low socioeconomic background, we still discharge according to older limit.
Estimation of occupational external exposure dose for a technologist using TLDs and pocket dosimeter in conventional nuclear medicine facility
Nisha Bhatia, Vandana K. Dhingra
Department of Nuclear medicine, Cancer Research Institute, Swami Rama Himalayan University Dehradun, India
Background and Aim: Routinely thermoluminescent detectors are used to record the prior external radiation exposure of occupational worker if the device is worn while working with radioisotopes emitting ionizing radiations so TLDs do not provide information in real time. But pocket dosimeters can provide the instant reading of exposure while working with radiation. So aim of the present study is to measure and compare occupational external exposure dose for a technologist using TLD and pocket dosimeter in conventional nuclear medicine facility. Material and Methods: External exposure dose of a single technologist dealing with 120GBq (3.2Ci) 99m Tc, 22.2GBq (600mCi) 131 I, 5.5GBq (150mCi) 153 Smused half yearly was measured using TLD as well as pocket dosimeter. Dose was measured for a technologist performed total of 798 clinical cases, covering the most common nuclear medicine procedures, including 400 bone scan, 139 thyroid scan, 190 renal studies, 24 myocardial perfusion studies and other scans, 39 Radioiodine therapy for hyperthyroidism and 6 remnant ablation, 2 patients of 153 Sm therapy for bone palliation. Dose for two technologists performed 99m Tc-WBC labeling procedure for single patient was also measured using pocket dosimeter. TLD badge worn for chest and wrist, and Pocket dosimeter was worn at chest level so that device should be audible. To estimate the effective whole body dose of technologist used pocket dosimeter at the times of radioisotopes dispensing, radiopharmaceutical preparations and administrations in addition to routine TLD wrist and chest badges. Results: The effective whole body dose to technologist measured by Pocket dosimeter was 1.07mSv, by TLD chest was 1.9mSv and TLD wrist was 4.25mSv. Dose received in a procedure of 99m Tc-WBC labeling by two technologists measured by pocket dosimeter was 6.08µSv (0.7mR) and 6.9µSv (0.8mR). Conclusion: Results shows that radiation dose received by single technologist performing all conventional nuclear medicine procedures are low and within permissible limits as prescribed by competent authority of India. Dose received by two technologists for 99m Tc-WBC labeling was also significantly low. Pocket dosimeter may underestimate the exposure dose but it can measure and display dose rate in real time. Pocket dosimeter can alert the worker when the dose exceeded by both visual and vibrating alarms. Pocket dosimeter should be worn in addition to routine TLD badges, it may reassure the exposure of the worker and helps in improving the work practice. All staff should be trained for proper use of personal dosimeters. Good work practice and safe handling of radioisotope can reduce the radiation exposure to the worker.
Radiation safety of the personnel during maintenance of liquid target post target foil rupture: An institutional experience
Munish Kumar, Ashwani Guleria * , Priya Bhusari, Dinesh Rawat, Rakhee Vatsa, Madan Parmar, Bhagwant Rai Mittal
Department of Nuclear Medicine and PET, Postgraduate Institute of Medical Education and Research, Chandigarh, *Wipro GE Healthcare
Background: Medical cyclotron is a compact cyclic particle accelerator used to produce positron emitters for preparation of PET imaging radiopharmaceuticals. Regular use of target in a busy work environment may lead to target foil rupture, which is one of the emergency situations requiring proper radiation safety during maintenance of the target since high levels of radiation exposures are associated with various components of target. In addition, scattered pieces of ruptured foil inside collimators or in vacuum chamber also contribute to the radiation exposure to the personnel. The emergency preparedness therefore must be planned to keep the radiation safety levels under prescribed limits. Aim: Optimization of radiation protection measures while handling of faulty target system. Materials and Methods: To minimize exposure to radiation, worker is advised to wait at least 24 hours before proceeding for maintenance work and should wear protective clothing, TLD dosimeter and pocket dosimeter for instantaneous dose measurements. At our institute, we carried out the radiation survey post target foil rupture during maintenance. After opening shielding doors, radiation levels around the target assembly were noted using a calibrated survey meter (RADMON 703A) to identify high radiation areas. The target body and extraction assembly were removed, kept behind L-bench with proper labeled warning symbols. The target body did not contain the ruptured fragments, therefore the radiation level was again measured in and around collimator as well as the vacuum chamber to locate the foil fragment. These fragments were then removed using long forceps. The tank was cleaned using liquid cleaner and tissue paper. Results: The target rupture was experienced after a total usage of 2322 µAh. It was observed that the radiation exposure at target surface with its intact ruptured foil was 866 mR/hr and after removal of the ruptured foil, the level declined to 56 mR/hr. The exposure level with the ruptured fragments inside the collimator was 212 mR/hr that decreased to 10 mR/hr after removing the fragments. Dose to the two radiation personnel involved in the maintenance was 63 and 21 µSv. Conclusion: The present study emphasizes the radiation protection to the personnel during the emergency situations in target maintenance. Proper radiation survey as described should be carried out in order to ensure that the dose to the personnel is within the prescribed limits of exposure in a single working day <80 µSv (interpolated to average annual limit for occupational worker i.e. 20 mSv).
Estimation of whole body radiation exposure to nuclear medicine personnel during synthesis of 177 Lu-labelled radiopharmaceuticals
Rajesh Kumar Mishra, Nishikant Avinash Damle, Praveen Kumar, Chandrasekhar Bal, Madhav Yadav, Rajeev Kumar, Sameer Taywade, Geetanjali Arora, Abhishek Behera
Department of Nuclear Medicine, All India Institute of Medical Sciences, New Delhi, India
Background: With rapid developments in the field of Nuclear Medicine Therapy, radiation safety of the personnel involved in the synthesis of these radiopharmaceuticals has become an integral part of it. Lutetium-177 is presently considered to be a versatile radionuclide for various therapeutic applications. Few studies have been done on this subject in western countries where comparisons have been made between, automated, semi automated and manual methods of synthesis of the radiopharmaceutical. However, data from the Indian subcontinent is scarce. Aim: To estimate whole body radiation exposure to the radiopharmacist involved in labeling of three different 177 Lutetium labeled compounds viz 177 Lu-DOTATATE, 177 Lu-PSMA-617 and 177 Lu-EDTMP. Materials and Methods: The department of Nuclear Medicine at A.I.I.M.S currently synthesizes three different Lutetium -177 labelled compounds viz 177 Lu-DOTATATE, 177 Lu-PSMA-617 and 177 Lu-EDTMP. A survey meter was used to measure background radiation before start of labeling procedure in the radiopharmacy by keeping it at the spot where the radiopharmacist normally stands during synthesis. A pocket dosimeter was then kept at the same spot for ten minutes to confirm the background radiation and the reading was subsequently scaled as per the time required for synthesis. The same pocket dosimeter was given to the radiopharmacist performing the labeling of 177 Lu-labelled compounds. All radiopharmaceuticals were synthesized by a single radiopharmacist with 3 years, 1 year and 3 years experience respectively in radiolabelling the above compounds. Results: 1Curie of 177 Lutetium Chloride was received fortnightly by our department. Data was collected for 6 syntheses of 177 Lu-DOTATATE, 4 syntheses of 177 Lu-PSMA-617 and 2 syntheses of 177 Lu-EDTMP. Mean time required to complete the synthesis was 46 minutes, 41 minutes and 4 minutes respectively. Mean whole body radiation exposure was 17.8 uSv, 9.5uSv and 1uSv respectively. The total exposure for all 12 procedures together was 147 uSv acquired over a period of 3 months with a fortnightly supply of 177 Lutetium to our institute. Highest exposure was obtained in the synthesis of 177 Lu-DOTATATE. Conclusion: Our initial data suggests that the whole body radiation exposure to the radiopharmacist in radiolabeling of 177 Lu-labelled radiopharmaceuticals is within prescribed limits for radiation personnel at the current synthesis frequency of once every fortnight. However for 177Lu-DOTATATE, it is higher than that reported for automated synthesis modules.
The strategically designed F-18 FDG(PET) hot lab can drastically reduce the whole body radiation exposure to medical personnel
Om Prakash, Swati Rachch
Department of Nuclear Medicine, The Gujrat Cancer and Research Institute, New Civil Hospital, Ahmedabad, Gujarat, India
Background: A combined F-18 FDG PET-CT scan provides both anatomical & metabolic information in single study, but the arrival of PET-CT in nuclear medicine dept. has raised the issue of radiation exposure to medical professional undertaking the preparation and administration of this radiopharmaceutical. the energy of γ-rays of 511 kev emitted by radionuclide are particularly challenging which gives very high dose to technologist as compared with nuclear medicine procedure. A number of simple but effective tools can be used to reduce to dose the time spent in hot area can be reduced by practice. Aim: The aim of the investigation was the identification of those working steps which deliver maximum radiation dose to worker and how to minimize the radiation dose. Materials and Methods: the study was conducted over a period of six months on 160 patients. F-18 multi- dose vial 100mci procured from cyclotron centre in Mumbai. The chest and wrist dose were measured for each working procedure during FDG handling by general and isolation method. Dose measurement by electronic pocket dosimeter PDM-117, the dosimeter and TLD were worn at all the time when performing the dispensing, measuring and injection. Two types of needle 1.5 inch and spinal needle used for dispensing. First of all patients isolated in injection room and iv cannulation done, first group pts. Got injection on injection table and another group injection done via a window just behind the L-Bench because after inj.pts. Also become a source of exposure. Most of the dispensing procedure done via spinal needle to avoid any contamination because from 1.5 we have to invert the tungsten vial. Results: When we gave the injection to pts. On inj. Chair the chest dose was 4.0±1.0µsv/pt. and rt. Wrist got 13.0±2.0µsv/pt. When same dose given to another isolated (behind L-bench & 11 inch solid concrete wall) patients the radiation dose to rt. wrist was 3.0±1.2µsv/pt. and total chest dose 3.0µsv/8 pts. The result shows that our wrist and chest gets maximum exposure in withdrawing and injecting the dose. On injection chair during injection pts. Become also a source of exposure which expose our whole body to avoid this we isolated the patient so that during injection only both side hands come in contact and this drastically reduced the radiation dose from 13µsv to 3µsv per pts. (78% reduced.) to wrist and average 0.4 µsv to chest(86% reduced). The photographs are showing this. Conclusion: We come on conclusion from this study in our centre that the use of spinal needle in withdrawal of isotope can avoid any spillage and isolate the patient before injection so that only hand from both side will come in contact. This process dramatically reduce the whole body exposure to medical professional.
Establishing Quality Assurance Framework for Radioactivity Measurement in Nuclear Medicine: An Important Measure towards Patient Safety
Pathak Subrata, Kar Soumyajyoti, Tandon Pankaj, Sonawane AU
Radiological Safety Division, Atomic Energy Regulatory Board, Mumbai - 400 094, India
Background and Aim: Use of unsealed radionuclides in Nuclear Medicine (NM) for diagnosis and therapy continues to increase steadily across the globe. It is of immense importance to optimise the administered activity in order to minimise the patient dose without compromising the required objective of diagnostic image quality or therapeutic efficacy. Radiation dose received by the patient is primarily determined by the amount of administered radioactivity and the chemical form of the radiopharmaceutical. The correctness of these factors plays an important role in ensuring safe and effective use of these drugs on patients. Radiopharmaceuticals should be characterized based on the contained activity, radiochemical and radionuclide purity. It is therefore important to establish a quality assurance (QA) programme for radioactivity measurements in nuclear medicine practices. Materials and Methods: In most of the developing countries, standard guidelines are not available for the end users so as to help them in developing and implementing Quality Assurance (QA) framework for radioactivity measurement. International Atomic Energy Agency (IAEA) published a guidance document, entitled ''Quality Assurance for Radioactivity Measurement in Nuclear Medicine'' (2006) which is a detailed and updated version of IAEA-TECDOC-602 published in 1991. This document addresses all the components necessary for developing and successfully implementing such QA programme in nuclear medicine facilities. ISO/IEC: 17025 also describes requirements for testing and calibration laboratories whereas IAEA safety standard series no. GS-R-3 gives emphasis on The Management System for Facilities and Activities. Our effort in this report is to bring out the core requirements of a simple and easily implementable QA framework for the end users, based on the documents mentioned. Results: In any practice, QA framework is mainly implemented to ensure the quality of the final objective, which, in case of nuclear medicine practice is the image quality or therapeutic efficacy without compromising patient safety. QA framework is mainly composed of two components. The first is the technical competence, and the other is the administrative procedures to avoid errors and even if it occurs, provides a means to document. IAEA, GS-R-3 recognised management systems as an important section of QA. The management requirements include commitment to QA, defining responsibilities of personnel, implementation of quality system, document control, nonconforming tests, and corrective/preventive actions. A chain of measurement traceability with at least one National Laboratory that maintains primary standards of radioactivity, has to be established by the management of a NM facility. In India, Radiation Safety Systems Division (RSSD) of Bhabha Atomic Research Centre (BARC) conducts National intercomparison of activity measurements of 131 I facilitating traceability to national primary standard by providing the calibrated 131 I capsules. In addition to the management requirements, for an effective QA framework, technical competence on the common radioactivity assay procedures is also very important. This section of the framework includes personnel training and documentation of qualifications, assays for radionuclide purity ( 99 Mo breakthrough), analysis of radiochemical purity (aluminium breakthrough), and measurement of radioactivity using radionuclide calibrators. Conclusion: To ensure patient safety a chain of measurement traceability with primary standards of radioactivity, is required to be established by the management of a NM facility. International guidelines available on QA framework for radioactivity measurement gives ample idea for setting up such framework. In this report a glimpse of the framework is presented, which will be useful for the management to prepare the blueprint of QA framework for ensuring patient safety.
Radiation Survey on Survey Meter, Swipe Sample With Dry Cotton And Swipe Sample With Wet Cotton
Gopinath R, Srikanth S, Agnes G, Madhusudhanan P, Dhanapathi H, Nandini Pandit
Department of Nuclear Medicine, JIPMER, Puducherry, India
Background and Aim: To survey radiation using survey meter and swipe sample methods (with dry cotton and wet cotton). Materials and Methods: Radiation survey meter, well counter, forceps, isopropyl alcohol, and cotton. Survey was taken in gamma camera room, gamma camera console room, injection room near L-bench and near fume hood. Radiation readings were taken with survey meter (RAM DA3-2000). Radiation survey measurements were observed to be at the background level without patient in gamma camera room, gamma camera console room and injection room. Radiation level varied with post-injected patients. Radiation levels were found to be more than background in L-bench, near fume hood because of handling high activity. So swipe sample method is very useful in these areas. This area was surveyed with swipe sample using dry cotton and wet cotton (isopropyl alcohol). Radiation survey was taken with survey meter at all places. Radiation survey was taken with dry cotton with area 900 cm 2 and counted with known efficiency of well counter (Biodex). Radiation survey was taken with wet cotton with area 900 cm 2 and counted with known efficiency of well counter (86%). Result: Survey meter reading is useful in gamma camera room, gamma camera console room, injection room. Swipe sample method is useful for areas near L-bench and fume hood. Swipe sample with wet cotton gives more value (counts) than sample with dry cotton. Conclusion: Swipe sample with wet cotton may give accurate value than swipe sample with dry cotton.
| Radiobiology|| |
Reversal of radiation induced apoptosis and oxidative stress in peripheral lymphocytes by supplementation of wheat grass extract in ratsexposed whole body exposure of X rays
Chandresh Shyam, Vijayta D. Chadha, D. K. Dhawan
Biophysics Department, Panjab University Chandigarh, India
Aim: Radiation induced ROS have unprecedented effects at molecular level in cells resulting in cell death, mutations, alteration of signal transduction which may later contribute to the development of cancer and hereditary diseases. One of the most significant detrimental effect of radiation is induction of cell death via apoptotic pathway after radiation exposure. Wheat grass extract has been reported to have a variety of beneficial effects including anti-inflammatory, antioxidant, antibacterial and anti-carcinogenic property.The current study was designed to evaluate radio protective efficacy of wheat grass extract against radiation induced apoptosis and oxidative damage in lymphocytes in rats exposed to fractionated dose of X rays. Material and Method: Animals were divided into four different groups: normal control group, X irradiated group (21 Gy fractionated dose of 3 Gy each day for 7 days), wheat grass treated group (80mg/100g body weight) and X-irradiated wheat grass treated group.Anti apoptotic studies were carried out by TUNEL assay and estimation of apoptosis marker enzyme activity ( caspase 3 and caspase 9). Estimation of cat,SOD, GPx, GSH and lipid peroxidation were also carried out in lymphocytes extracted from whole blood. Results: Significant increase in number of apoptotic lymphocytes cells was observed in the irradiated animals. This observation was in coordination with the increased activity of apoptosis marker enzymes caspase 3 and caspase 9. However, pre-treatment with wheat grass extract provided protection against radiation induced apoptosis as observed by decrease in apoptotic lymphocytes and decreased activity of apoptotic marker enzymes. Further, the lymphocytes from irradiated rats showed increase in levels of lipid peroxidation which was accompaniedby significant decrease in the activity of SOD, CAT and GPx. Pretreatment with wheat grass restored activity of enzymes involved in oxidative stress and decreased lipid peroxidation in irradiated cells. Conclusion : The current study shows wheat grass to be effective radioprotector against X ray induced genotoxicity and oxidative stress.
| Radiopharmacy|| |
Validation of Fractionation Method of 99m Tc-MDP Radiopharmaceutical
Vasumathi, Ramandeep B, Arunkumar T, Sibi O. Shivananda B, Rajesh K
Department of Nuclear Medicine, School of Allied Health Science, Manipal University, Manipal - 576 104, Karnataka
Background: Tc 99m Methylene diphosphonate (MDP) has rapid blood clearance, excellent in vivo chemical stability, and a high bone-to-soft tissue ratio, which are ideal for bone imaging. Maximum centers follow the fractionation method for economical purpose. But it has not been standardized yet. Therefore there is a need for validation scientifically and ethically. Aim : Validation of fractionation method of 99m Tc-MDP radiopharmaceutical. Materials and Methods: BRIT pharmaceutical MDP kit(contains 10mg MDP, 5mg NaCl, 0.5mg-Gentisic acid,0.6mg-Stannous chloride), 99m Tc-pertechnetae, pH Paper, Radiochemical purity test unit, Sterility test unit and other accessories like vial, syringe, etc.
- To fractionate 99m Tc-MDP using vial and syringe fraction technique
- 1.7ml normal saline will be added to MDP vial (mother vial).0.2ml will be fractionated into 8 sterile vials, one vial will be used immediately and others will be kept at 0○ C
- 18mCi of sodium pertechnetate (NaTcO 4 ) is added into the fractionated vial and kept for incubation for 10 mins.
- Similar procedure is done for other fractionated vials.
Physical appearance; pH; Radiochemical purity; Sterility test.
- 1.7ml normal saline will be added to MDP vial(mother vial) and kept at 0°C for future use
- 0.2 ml of MDP is fractionated from mother vial into a sterile syringe and 18mCi(0.2mL) of NaTcO 4 is added into the same syringe followed by incubation for 10 Mins. Similar procedure is adopted for the rest of the days
- Reconstituted in syringe and vial will undergo following quality control checks
We analyzed the data 2 nd to 8 th days of each 5 cycle for vial and syringe fractionation method separately and calculated acceptance rate of vial and syringe fractionation method for each of all 5 cycle. These results were compared with the standard protocol suggested by BRIT for formulation of Tc 99m radio pharmaceuticals. Results : All quality parameter are within the accepted range (no variation) except %RCP parameter in both syringe and vial method (accepted range %RCP >96%). Average days that can be fractionated in vial method is 3 days and in syringe method is 2 days. Conclusion: Fractionation method for 99m Tc-MDP radiopharmaceutical can be standardized for 3 days and 2 days for vial and syringe method respectively.
Semi Automated Separation and purification module of 68 ge/ 68 ga generator for ready to use at hospital
Sankha Chattopadhyay, Sujata Saha Das, Madhusmita, Md. Nayer Alam, Luna Barua, Umesh Kumar, Asit Pal
Radiopharmaceutical Lab., Regional Centre, Board of Radiation & Isotope Technology, VECC, Kolkata, India
Background and Aim: 68 Ga is an emerging radiotracer for PET imaging. The 270 days half life of parent Germanium-68 provides the shelf life of the 68 Ge/ 68 Ga generator for one year and allows daily multiple elution of Gallium-68. Production of 68 Ge in the VECC cyclotron has been carried out from nat Ga target for indigenous fabrication of 68 Ge/ 68 Ga generator based on SnO 2 inorganic matrix. Since 68 Ga is being eluted from the column with 1N HCl, this initial 68 Ga eluate require post-elution purification processing to achieve the required chemical, radiochemical and radionuclidic purity of 68 Ga to allow for efficient synthesis of 68 Ga radio pharmaceuticals. The whole process has been semi-automated for efficient, rapid and easy handling of the generator. Materials and Methods : 68 Gewas produced by nat Ga (p, 2n) 68 Ge reaction in VECC cyclotron. The irradiated target was dissolved in dil. HCl and H 2 O 2 .The parent isotope 68 Ge can be separated from the target matrix by solvent extraction or can be directly loaded on the SnO 2 column (1g, 100-150 mesh). The column was washed with sufficient quantity of 1M HCl to ensure complete removal of inactive Ga and Zn isotopes. Then 68 Ga was eluted from the column daily with 4ml 1M HCl and this was further diluted with water for post elution purification on a tiny Dowex-50 (25 mg) cation exchange resin column. Then the column was washed with acetone-HCl mixture followed by water. Finally, the trapped 68 Ga was eluted with 1M NaOH which was collected in a vial containing acetic acid. Results: 68Ge production rate at EOI was about 3.6μCi/μAh (n=3). The separation of 68 Ge parent from the irradiated Ga target was achieved using SnO 2 column. Elution efficiency of the generator was 55% (n=317). The average yield of purified 68 Ga was around 80% ± 8% (n=317). Average percentage of the loaded 68 Ge activity broke through the column was 0.014 and 0.00027 before and after purification, respectively (n=317). The pH of the final preparation was 6.5. Conclusion: It may be concluded that the newly developed semi automated module for separation and purification of 68 Ge/ 68 Ga generator can give sufficient 68 Ga activity of required radionuclidic purity for preparation of radiopharmaceuticals. In the forthcoming DAE Medical cyclotron, Kolkata the indigenously available 68 Ge/ 68 Ga generator would be a boon to the nuclear medicine fraternity in our country.
Production of 89 Zr from nat Y target by proton irradiation in VEC cyclotron and separation by Dowex-1 anion exchange chromatography
Sujata Saha Das, Luna Barua, Md. Nayer Alam, Madhusmita, Asit Pal, Umesh Kumar, Sankha Chattopadhyay
Radiopharmaceutical Lab., Regional Centre, Board of Radiation and Isotope Technology, VECC, Kolkata, India
Background and Aim: Positron emission tomography (PET) imaging with radiolabeled monoclonal antibodies has always been a dynamic area in molecular imaging. 89 Zr has favorable physical characteristics for antibody-based imaging, with a half-life of 78.4 h and a relatively low positron energy of 395.5 keV, and its advantages over the alternatives are manifold. The ideal physical characteristic of 89 Zr is suitable for labeling with monoclonal antibodies which in turn convert it as a suitable candidate for immune-PET imaging. The aim of the study is to produced 89 Zr from nat Y in VECC cyclotron and standardize separation chemistry to get highly pure 89 Zr. Materials and Methods: Natural Yttrium foil was irradiated in VECC cyclotron with 12 MeV, 1µA proton beam for 22h duration for production of 89 Zr.The irradiated target was dissolved in Conc. HCl. Anion exchanger Dowex -1 resin was used as a column for the separation of 89 Zr from irradiated Y target. After loading the dissolved target, the column was washed with conc. HCl. 89 Zr activity remained bound to the resin, whereas Y freely comes out of the column which was monitored by 88 Y radiotracer. The bound 89 Zr activity was eluted from the column with dilute HCl and collected in 2ml fraction. 89 Zr activity in dilute HCl obtained from the column was evaporated to dryness and reconstituted in 10% sodium carbonate solution for labeling. It was mixed with requisite amount of oxine in chloroform and made vortex for 15min. The chloroform phase was separated from the aqueous phase, dried with anhydrous sodium sulphate, evaporated and the residue obtained reconstituted with saline. Results: The experimental yield of 89Zr was 7mCi (0.5mCi/μAh) at EOB. The recovery yield of 89 Zr activity from the column was found > 98 %. The 88 Y activity was not detected in the 89 Zr eluted fractions by HPGe detector. The labeling yield was > 93% and radiochemical purity (RC Purity) of the [ 89 Zr]-oxine complex was above 95%. Conclusion: This work shows that 200mCi of 89Zr can be produced with 20μA proton beam of 12MeV for 20h irradiation. The advantage of this production route is that natural Y has only one stable isotope i. e., 89 Y. The successful labeling of the separated 89 Zr with oxine proves that the the Dowex-1 anion-exchange separation method can produce 89 Zr of suitable purity for labeling with monoclonal antibodies.
Stability Study to Evaluate the Shelf Life Extension of Phytate (TCK-16) Cold Kit of BRIT
Ashok R. Chandak, R. Krishnamohan , Barakha Karkhanis, S. S. Sachdev, M. G. R. Rajan*
Radiopharmaceutical Programme, Board of Radiation and Isotope Technology, BRIT-BARC Vashi Complex, Navi Mumbai - 400 073, *Radiation Medicine Centre,BARC, Parel, Mumbai, India
Background and Aim: BRIT has indigenous facility to prepare and supply cold kit for 99m Tc-Phytate injection (TCK-16), used for static liver imaging and the shelf life of the kit is six months. The short shelf life of the kit necessitates planning production after every three months and frequent analysis of the product as well as inconveniencing to end users in terms of having to place frequent requisition orders for the kit. Expired kits remains unused owing to its short shelf life at the user side and also waste of economy. In order to attend these problems it was decided to check the possibility of increasing the shelf life of this kit, by carrying out physicochemical and biological tests for six consecutive batches of the product for the period of 18 months. Materials and Methods: The physicochemical evaluations were carried out at periodic intervals of two months and biological tests (ST, Pyrogen test and BD) were carried out at 6, 12 and 18 months from the date of production. Phytate kit was labeled with upto 50 mCi (maximum 3 ml) of 99mTc-sodium pertechnetate, derived from Coltech and Autosolex Generator of BRIT. The labeled kit were evaluated for appearance, pH, RCP, ST, Pyrogen test and BD as per the RPC monograph. Appearance of reconstituted phytate injection was observed and pH was tested with universal indicator pH paper. Radiochemical purity test was carried out by ascending paper chromatography using Whatman 1 chromatography paper as support, 85% methanol as solvent and developing the chromatogram upto a solvent front of 15 cm. The ST and pyrogen tests were carried out by Invochem Lab, Mumbai. Results: It was observed that the appearance of the labeled kit injection of all batches of the product at the various time intervals studied, and was found clear and colorless, pH was between 5.5 and 6.5, and RCP was above 95% for 18 months. The ST, Pyrogen study showed that it passes the parameters and BD also showed desired results for the product up to 18 months. Conclusion: The stability study of kit for Tc-Phytate (TCK-16) indicates that the shelf life of the kit can be extended to 12 months, after necessary regulatory approval.
Reactor production and electrochemical purification of 169 Er: A potential step forward for its utilization in in vivo therapeutic applications
Rubel Chakravarty, Sudipta Chakraborty, Viju Chirayil, *Ashutosh Dash
Isotope Application and Radiopharmaceuticals Division, Bhabha Atomic Research Centre, Trombay, Mumbai - 400 085, India.
Background and Aim: The aim of the present study was to develop and demonstrate a viable method for the reactor production of 169 Er with acceptable specific activity using moderate flux reactor and its purification from 169 Yb following electrochemical pathway based on mercury-pool cathode to avail 169 Er in radionuclidically pure form essential for its therapeutic use. Materials and Methods: Erbium-169 was produced in reactor by neutron bombardment of isotopically enriched (98.2% in 168 Er) erbium target at a thermal neutron flux of ~8΄10 13 n.cm -2 .s -1 for 21 d. A thorough optimization of irradiation parameters including neutron flux, irradiation time and target cooling time was carried out. The influence of different experimental parameters for the quantitative removal 169 Yb from 169 Er was investigated, optimized and based on the results; a two-cycle electrochemical separation procedure was adopted. The suitablility of purified 169 Er for application in radiation synovectomy and bone pain palliation was ascertained by carrying out radiolabeling studies with hydroxypaptite (HA) particles and 1, 4, 7, 10-tetraazacyclododecane-1, 4, 7, 10-tetraaminomethylene phosphonic acid (DOTMP), respectively. Results: Thermal neutron irradiation of 10 mg of isotopically enriched (98.2% in 168 Er) erbium target at a flux of ~8΄10 13 n.cm -2 .s -1 for 21 d followed by a two-step electrochemical separation of 169 Yb impurity yielded ~3.7 GBq (100 mCi) of 169 Er with a specific activity of ~370 MBq/mg (10 mCi/mg) and radionuclidic purity of >99.99%. The reliability of this approach was amply demonstrated by performing several production batches, where the performance of each batch remained consistent. The utility of the purified 169 Er was demonstrated in the radiolabeling studies with HA particles and DOTMP, wherin both the radiolabeled products were obtained with high radiolabeling yield (>99%). Conclusions: A viable strategy for the batch production and purification of 169 Er, suitable for therapeutic applications, has been developed and demonstrated.
Evaluation of MDP (TCK-30) Cold Kit of BRIT for the Shelf Life Extension Study
Ashok R. Chandak, Sangeeta H. Joshi, R. Vanaja,
S. S. Sachdev, M. G. R. Rajan*
Radiopharmaceutical Programme, Board of Radiation and Isotope Technology, BRIT-BARC Vashi Complex, Navi Mumbai - 400 073, *Radiation Medicine Centre, BARC, Parel, Mumbai, India
Background and Aim: BRIT has indigenous facility to prepare and supply cold kit for 99m Tc-MDP (Methylene diphosphonic acid) injection (TCK-30), used for bone imaging and the shelf life of the kit is ten months. Expired kits remains unused owing to its short shelf life at the user side and also waste of economy. The short shelf life of the kit necessitates planning and production every month and frequent analysis of the product as well as inconveniencing to end users in terms of having to place frequent requisition orders for the kit. In order to attend these problems it was decided to check the possibility of increasing the shelf life of this kit, by carrying out physicochemical and biological tests for six consecutive batches of the product for the period of 24 months. Materials and Methods: The physicochemical evaluations were carried out at periodic intervals of two months and biological tests (ST, Pyrogen test and BD) were carried out at 6, 12 and 18 months from the date of production. MDP kit was labeled with upto 100 mCi (maximum 3 ml) of 99mTc-sodium pertechnetate, derived from Coltech and Autosolex Generator of BRIT. The labeled kit was evaluated for appearance, pH, RCP, ST, Pyrogen test and BD as per the RPC monograph. Appearance of reconstituted MDP injection was observed and pH was tested with universal indicator pH paper. Radiochemical purity test was carried out by ascending paper chromatography using Whatman 1 chromatography paper as support, 85% methanol and 0.5 M Acetate buffer (pH 5.0) as solvent and developing the chromatogram upto a solvent front of 15 cm. The ST and pyrogen tests were carried out in rabbits by Invochem Lab, Mumbai. Results: It was observed that the appearance of the labeled kit injection of all batches of the product at the various time intervals studied, and was found clear and colorless, pH was between 5.5 and 6.5, and RCP was above 95% for 24 months. The ST, Pyrogen study showed that it passes the parameters and BD also showed desired results for the product up to 24 months. Conclusion: The stability study of kit for Tc-MDP (TCK-30) indicates that the shelf life of the kit can be extended to 18 months, after necessary regulatory approval.
Extension of shelf life of kit for the preparation of 99m Tc Diethylene triamine penta acetic acid of BRIT
Archana S. Ghodke, R. Krishnamohan, R. Vanaja, S. S. Sachdev
Radiopharmaceutical Programme, Board of Radiation and Isotope Technology, BRIT-BARC Vashi Complex, Navi Mumbai - 400 703, India
Background and Aim : Board of radiation and isotope technology has been regularly supplying the kit for the preparation of 99m Tc-DTPA used for renal studies to Nuclear Medicine centres for the past 40 years. The shelf life of this kit had been fixed as 6 months from the date of manufacturing. In order to make the kit more user friendly, a work was taken up to confirm whether shelf life can be increased to more than 6 months. This would benefit both us at BRIT as manufacturer for scheduling production and the Nuclear Medicine community for extended use of the kit. Materials and Methods : Six consecutive batches were evaluated for critical parameters namely pH, clarity, radiochemical purity and bio-distribution studies for a period of 25 months as per RPC monograph. The physico chemical tests were carried out at periodic intervals up to 25 months and biological test (ST, Pyrogen test and BD ) were carried out at 13 months and 25 months from the date of manufacturing. DTPA kit was labeled with 99m Tc- sodium pertechnetate ( 15-20 mCi/vial) derived from Coltech generator of BRIT. The Radiochemical Purity test was carried out by ascending paper chromatography using whatman no1 chromatography paper as support in 85% methanol after 10 mins incubation. Results : The Radiochemical purity was well above 90% during the period of studies. Bio-distribution studies were carried out in swiss mice and the result showed satisfactory results with no signs of deterioration of the product. Therefore this kit can be safely used for patient studies even upto 24 months. These promising results have prompted to consider the extension of shelf life of this kit after necessary regulatory approval. Conclusion : The performance of the kit for 99m Tc-DTPA is satisfactory for a period of 25 months and hence the shelf life of the kit can be extended upto 24 months after the approval by the regulatory body.
Extension of shelf life of kit for the preparation of 99m Tc (V) - Dimercapto Succinic Acid (DMSA)
H.Sheela Muralidharan, Pramod Dhodkhe, R.Vanaja, S.S.Sachdev
Radiopharmaceutical Programme, Board of Radiation and Isotope Technology (BRIT), BRIT-BARC, Vashi Complex, Navi Mumbai - 400 703, India
Background and Aim: Board of Radiation and Isotope Technology (BRIT) has been supplying the kit for the preparation of 99m Tc (V)-DMSA (Code: TCK-35) for more than three decades. It is a two component kit, component A contains the ligand DMSA and stannous chloride at pH 2.5 and component B contains NaHCO 3 (3.5%) in freeze dried form. 99m Tc (V)-DMSA is formed in alkaline pH and is used for tumour scintigraphy. Currently, the expiry period of kit for 99m Tc (V)-DMSA is 6 months from the date of production.Nuclear physicians have often expressed their desire to increase the expiry period so that they can use the kit for a longer period and from the production point of view the frequency of the production of the kit can be reduced if the kit has a longer shelf life. Keeping this in mind, work was undertaken to increase the shelf life of the kit. Materials and Methods : 100 vials from six consecutive batches were kept aside for stability studies. The radiolabelling procedure involves the addition of 99m Tc sodium pertechnetate to component A and immediate addition on 0.2 ml of component B (which is reconstituted with 1 ml water for injection) to the component A which is the reaction vial. The formulation is incubated for 10 minutes at room temperature. 99m Tc (V)-DMSA prepared from all the six batches were evaluated for its appearance, pH, sterlity and apyrogenicity as per RPC monograph. The kit was assayed for its Radiochemical purity (RCP) by a two solvent paper chromatography system using 1 mm whatman paper in 85% methanol and saline to asses the pertechnetate and reduced hydrolysed technetium impurities respectively. The physico chemical tests (PCT) were done every month beyond six month of production of the kit. Results: It was found that the physical appearance of 99m Tc (V)-DMSA prepared from all the six batches was clear and colourless, pH was 7.0-8.0 and RCP was above 95% for 13 months, the period of study. All the six batches were passing in the pyrogen and sterility tests also. Conclusion: As the studies showed that the kit is stable for more than one year, the shelf life of kit for the preparation of 99m Tc (V) - Dimercapto Succinic Acid (DMSA) can be increased to one year after the approval from the Radiopharmaceutical Committee (RPC).
Microwave assisted synthesis of 131 I labeled meta iodobenzyl guanidine (MIBG)
Kiran S. Mehra, Richa Tiwari, Anand Gaurav, A. Thulasidhasan, Ravi Seshan and S. S. Sachdev
Radiopharmaceuticals Programme, Board of Radiation and Isotope Technology (BRIT), BARC Vashi Complex, Sector-20, Navi Mumbai - 400 703, India
Background and Aim: To develop a method kit for the synthesis of iodine labelled MIBG. 123/125/131 I-MIBG can be synthesized by the followingnucleophilic exchange reactions: Most of the nucleophilic exchange reactions use highreaction temperature and long heating time. Under these reactionconditions, both radiochemical purity and labeling efficiencyare reduced. The Cu + assisted nucleophilic exchange reactionis the mildest reaction condition for radioiodination of molecules. In our study we have used these reaction conditions to prepare 131 I labelled meta iodobenzyl guanidine. Microwave heating has been used to accelerate chemicalreactions. Method: To solution of MIBG in ethanol (0.087µg, 0.34 nmole), CuSO 4 .5H 2 O (0.69 µg, 2.86 µmole), Na 2 S 2 O 5 (596 µg, 3.14 µmole) and Na 131 I (50 mL , 37 MBq, specific activity ~20 Ci/mg of iodine) was added and the pH was adjusted to ~4 using glacial acetic acid. The reaction mixture was heated to a temperature of 100 0 C in 2 min using a microwave reactor ( microwave chemical synthesiser, milestone make) and maintained at this temperature for 4 minutes. After cooling, 1 mL of 0.76 M sodium acetate solution was added to the reaction mixture. The labeled product was separated from unreacted iodide using dichloromethane. The organic extract was flushed with nitrogen to remove dichloromethane and reformulated in 5% ethanol. Result and Conclusion: The microwave heating method significantly reduces radiochemical and chemical impurities, due to the shorter heating time. The labelling efficiency was >95%, and the radio chemical purity was >98% determined by TLC (silica gel ,C 2 H 5 OH :10% NH 4 OH 3: 1 v/v, R f MIBG 0.16 and Na 131 I 0.95). The method adopted here is best suited for the development of KIT for the synthesis of iodine labelled MIBG.
Studies on Antibody Affinity Constants on Operational Aspects of Liquid Phase and Solid Phase RIA Development
Shripriya Purohit, Vijay Kadwad, Jayula Sarnaik, Rani Gnanasekar, Shalaka Paradkar and Satbir Singh Sachdev
Radiopharmaceuticals Programme, Board of Radiation and Isotope Technology (BRIT), BRIT Vashi Complex, Navi Mumbai - 400 703, Maharashtra, India
Background and Aim: Detection limit or sensitivity in radioimmunoassay (RIA) is mainly governed by titre, affinity and specificity of the antibody. It is presumed that apart from the optimal dilution, the affinity constant of the antibody is not subject to modification by normal chemical manipulations. However, removal of large concentration of endogenous antigens associated with conventionally produced antibodies is believed to increase the affinity of the antibody. In order to achieve optimal assay results, it is essential to know the affinity constants obtained by liquid phase and solid phase assays using raw, purified or solid phase bound antibodies. Materials and Methods: In-house magnetizable cellulose and polyclonal antibodies for T3 and T4 were used. Both the antibodies were covalently linked to OH groups present on the magnetizable cellulose particles for the development of solid phase assays. Rest of the reagents required for setting up of the assays and Scatchard plots were part of RIA kits for T3 and T4 supplied by BRIT with minor modifications. Antibodies were purified using conventional salt precipitation method followed by the dialysis. Affinity constants of antibodies were calculated from respective Scatchard plots for raw, salt precipitated/purified and magnetizable cellulose bound antibodies using their optimal dilutions. Results: Standard curves were constructed from the data obtained with raw and purified antisera at the same working dilutions. The same data was recalculated to construct the Scatchard plots. Affinity constants derived from these plots in the case of T4 antisera were 2.0 x 10 11 litre/mole and 3.90 x 10 11 litre/mole for raw and purified antiserum respectively. In the case of T3 antiserum affinity constants obtained were almost identical: 1.60 x 10 12 litre/mole (raw) and 1.55 x 10 12 litre/mole (purified). The affinity constant has almost doubled in the case of T4 antiserum after purification whereas it remained constant in the case of T3 antiserum. However, drastic reduction in affinity constants of solid phase antibodies were observed in both the cases. T3 and T4 antibodies linked to magnetisable particles exhibited affinity constants of 1.53 x 10 11 litre/mole and 1.93 x 10 10 litre/mole respectively. Conclusion: Knowing the affinity constant of an antibody allows judicious selection of antibody for a specific purpose. In some cases, affinity constant of the antibodies can be increased significantly by purification and can be used in sensitive assays such as free hormone assays. Purified antiserum with high affinity constant is desirable in the development of solid phase immunoassays as there will be a significant reduction in the affinities of the antibodies upon linkage to the solid supports.
No-carrier added * I-meta-iodobezylguanidine suitable for clinical use: Synthesis and separation studies from its precursor meta-trimethylsilylbenzylguanidine
B. K. Tiwary, Vrinda PC, Anupam Mathur, V. V. Murhekar, S. S. Sachdev
Board of Radiation and Isotope Technology, Mumbai, India
Background and Aim : 131 I-Meta-iodobezylguanidine (mIBG) is a proven theranostic agent selectively used for targeted radiotherapy of tumors such as phaeochromocytoma and neuroblastoma. Both carrier added and carrier free preparations are in clinical use worldwide. However, the synthesis and isolation of the latter preparation remotely from its precursor in bulk quantities for patient use (> 100 mCi) is highly challenging. This paper describes preliminary studies in the preparation of carrier-free 125- I-meta-iodobezylguanidine using precursor meta trimethylsilylbenzylguanidine. Materials and Methods : Two different labelling approaches; peracid and chloramine-T oxidation were evaluated using 2-3 µmol of precursor and around 300 µCi of I-125 as NaI. The product was purified using a Dowex ion-exchanger to remove unreacted 125 I - . This was then analyzed by HPLC and purified using C-18 cartridge (10 µm particle size) to remove unreacted m-trimethylsilyl benzylguanidine from the radiolabeled mIBG. Results : Radiochemical yield determined using electrophoresis and HPLC characterization was more than 90% in both the cases. The labelled product was purified using C 18 cartridge using triethyl ammonium phosphate buffer (0.3 %, pH 4) where different fractions of 1mL each were collected to determine the separation of labelled 125 I-mIBG from its precursor. The precursor eluted out completely in two fractions whereas subsequent fractions showed the presence of radiolabelled product only. Though, 40% of the radiolabeled activity was found to overlap with the precursor material in first two fractions, remaining 60% of the labelled product was of nca-level as determined by HPLC. Conclusion : nca- 125 I-mIBG obtained is suitable for clinical use and is easily adaptable for mass scale production. However, further steps are underway to increase the separation efficiency of labelled mIBG and its precursor trimethylsilyl derivative.
Development of 99m Tc-Labelled Cefprozil - An Infection Imaging Agent
Sangeeta H. Joshi 1 , Sujith Sukumaran Nair 2 , D. Padmanabhan 1 , Grace samuel 1
1 Radiopharmaceutical Programme, Board of Radiation and Isotope Technology, BRIT-BARC, Vashi Complex,Navi Mumbai, 2 School of Biotechnology and Bioinformatics, D. Y. Patil University, Nerul, Maharashtra, India
Background :In the quest of effective infection imaging agent we tried radiolabelling Cefprozil, a second generation Cephalosporin antibioticwith 99m Tc. Earlier many other labelled antibiotics have been developed for infection imaging, with varying degrees of success. Ciprofloxacin is one such antibiotic which is extensively studied. However, quite a few reports state that Ciprofloxacin is not as infection specific as desired. On the other hand superiority of 99m Tc-Cefprozil as an infection imaging agent has been reported (Journal of Analytical Science and Technology 2014, 5:32). Aim : To develop 99m Tc-labelled Cefprozil to use as an infection imaging agent. Method : We labelled Cefprozil in our laboratory using 99m Tc. The labelling protocol using SnCl 2 .2H 2 Oas a reducing agent was standardised and the labelled product was scrutinized for its quality. Cefprozil (4 mg) was labelled with 200-400 MBq 99mTc-sodium pertechnetate (1ml) using 100 μg of SnCl2 .2H 2O (50 μl).pH of the reaction mixture was critically adjusted to 4using 0.1 N HCl prior to addition of stannous chloride. The mixture was incubated for 30 min. at room temperature. 99m Tc-Cefprozil was subjected to extensive Quality Control analysis. Stability of the labelled compound was studied up to 24 h. An in vitro bacterial binding study of 99m Tc-Cefprozil was done using a pure strain of Staphylococcus aureus (ATCC- 6538). Results: The radiochemical purity of 99m Tc-Cefprozil, was 90 ± 2%. Maximum binding of 38.7% was observed after overnight incubation at 37 0 C. Decreased Bacterial binding of 99m Tc-Cefprozilin presence of an excess of non-radioactive Cefprozil confirms the specifictity of labelled Cefprozil towards the bacteria. Conclusion: Initial reports are promising, indicating that, 99m Tc-Cefprozil could be efficiently used for infection imaging. Further studies to prove the specificity of 99m Tc-Cefprozil towards bacterial infections over sterile inflammation are in progress.
Fluorine-18 PET Tracer for Diagnosis of Alzheimer's Disease
Lakshminarayanan N* 1 , Arun Manikrao Bhusari 2 , Mariam Sohel Degani 2 , Harish Shashikant Kundaikar 2 , Harikesh Nandkishor Janmanchi 2 , M.G.R. Rajan 1
1 Radiation Medicine Centre, Tata Memorial Hospital, BARC, Parel, Mumbai-12, India, 2 Department of Pharmaceutical Sciences and Technology, Institute of Chemical Technology, N.P.Marg,Matunga (E), Mumbai-19, India
Background and Aim: 1. Design of molecules for interaction with amyloid beta(Aß) fibrils, with suitable properties to penetrate Blood-Brain Barrier (BBB), 2. Synthesis of designed molecules and screening them for Aß fibril binding property, 3. F-18 radio-labelling of the suitable molecule and its purification and 4. Bio-distribution study of F-18 labelled molecule in Wistar rat and rabbit and its PET imaging. Materials and Methods: The molecules were designed on the basis of ligand based drug design (LBDD) and structure based drug design (SBDD) studies using computational drug design modules. The designed molecules were synthesized using cold fluorination and characterised by IR, NMR and MS. The Log P value of molecules was determined using HPLC. In vitro binding study of molecules with Aß fibrils was carried out using Thioflavin T (ThT), at excitation and emission wavelength at 440 nm and 480 nm respectively.The precursor of most active molecules in ThT assay was [F-18]radio-fluorinated and purified by Solid phase extraction method. The labelled molecules were studied for in-vivo bio-distribution and PET/CT imaging in Wistar rat and rabbit respectively. Results: The molecules showed similar alignment and similar pharmacophoric elements to that of reported Aß plaque binding molecules. The experimentally calculated log P values are similar to the predicted values. In ThT assay, one of the fluorinated molecules had shown best binding potential with Aß fibrils. The radio-fluorination yield for the precursor of most active molecule was > 60%. The radiolabeled molecule had good BBB penetration in Wistar rat and rabbit. Conclusion: LBDD and SBDD study assisted in the understanding of pharmacophoric elements in molecules necessary for the Aß fibrils binding. In vivo evaluation of [F-18]-labelled molecule in Wistar rat and rabbit showed good BBB penetration property, thereby indicating that the molecule has a potential to be used for imaging AD.
DOTA-Zoledronate a novel bone seeking compound for Ga-68 PET Diagnosis and Lu-177 Endoradiotherapy of bone metastases: From preclinical to first human results.
Marian Meckel 1 Mike Sathekge 2 , Wolfgang Mohnike 3 , Frank Rφsch 1
1 Institute of Nuclear Chemistry, Johannes-Gutenberg-University Mainz, Fritz-Strassmann-Weg 2, 55128 Mainz, Germany, 2 Department of Nuclear Medicine, University of Pretoria & Steve Biko Academic Hospital, Pretoria, South Africa, 3 Diagnostisch-Therapeutisches Zentrum, DTZ am Frankfurter Tor, Berlin, Germany
Background and Aim: DOTA based bisphosphonates showed first promising results in patients suffering from bone metastases. When labeled with generator derived Ga-68 it enables high qualitative skeletal PET-scans for hospitals or even small nuclear medical facilities without a cyclotron infrastructure. Furthermore, DOTA based bisphosphonates are able to be used as therapeutic agents for the treatment of painful bone metastases, when labelled with low energy ß-emitter Lu-177. Zoledronic acid is currently the most potent bisphosphonate in clinical use. Here we report the development of the novel DOTA zoledronic acid derivative suitable for Ga-68 PET Diagnosis and Lu-177 radiotherapy and its first in-men application. Materials and Methods: The novel DOTA-Zoledronate (DOTAM ZOL ) was successfully synthesized and labelled with Ga-68 and Lu-177 and evaluated in in vitro and in vivo studies in Wistar rats. The Ga-68 labelled analogous [Ga-68]DOTAM ZOL was further used to perform a first in-men study in a male prostate cancer patient suffering from bone metastases. The SUV max values in skeletal lesions and soft tissues like the liver, kidneys and salivary glands were compared to a previously done [Ga-68]HBED-PSMA scan. First applications of [Lu-177]DOTAM ZOL in 10 patients suffering from bone metastases of different origin were performed with subsequent whole body scintigraphies at different time points after injection. Results: The novel theranostic bisphosphonate DOTA-Zolendronate showed excellent radiolabeling yields with Ga-68 and Lu-177 and can be easily implemented in routine clinical use. [Ga-68]DOTAM ZOL and [Lu-177]DOTAM ZOL showed a very similar distribution in the rat model with a total skeletal retention of almost 50 %ID, which is very similar to those [F-18]NaF. The compound showed fast blood clearance and renal excretion pathway. First human PET results showed an excellent target-to-background ratio superior to radiolabelled PSMA in context of bone lesions. The SUV max in bony lesions was obviously higher for DOTAM ZOL (e.g. L2 vertebra SUV max =68.9) compared to PSMA (e.g. L2 vertebra SUV max =8.8). First applications of [Lu-177]DOTAM ZOL in metastatic patients showed strong accumulation of the therapy compound in bone lesions determined by planar scintigraphic images and SPECT/CT. In an individual application the PSA value of a prostate cancer patient decreased from 478 ng/mL to 88 ng/mL two month after he received a single treatment with 5.5 GBq [Lu-177]DOTAM ZOL . Conclusion: The novel DOTA-Zoledronate DOTAM ZOL showed promising results in preclinical studies and in first patient applications. The theranostic Ga-68/Lu-177 concept shows currently excellent results in the treatment of neuroendocrine tumors. The compound DOTAM ZOL extends this concept for a promising bone metastases treatment.
Tracing the path of the 68 Ga labeled radiopharmaceutical & predicting its possible outcome in a IQS 68 Ga Fluidic Labeling module
Priya Monteiro, Bhakti Shetye, Mehjabeen Pathan,
Dr. Archi Agrawal, Dr. Nilendu Purandare, Dr. Sneha Shah, Dr. V. Rangarajan
Department of Nuclear Medicine and Molecular Imaging, Tata memorial Hospital, Mumbai, Maharashtra, India
Background : The IQS Ga68 Fluidic Labeling module by ITG comprises a Ge 68 -Ga 68 generator with synthesis unit and is a self-shielded unit .Once the fluidics are set up and the shielded lid is in place, the entire procedure has to be performed without any verification of whether the steps followed will result in expected product yield. This was the rationale for doing this study. Aim: To trace the path of the radioactivity by measuring the surface dose-rate over the self-shielded IQS Ga68 Fluidic Labeling module by ITG. Materials and Methods : The IQS Ga68 Fluidic Labeling module by ITG allows access through 3 openings to 5 important components (reactor, cartridge, generator, waste vial, product vial) in the preparation of the labeled product. The survey meter used was a Rotem Ramgene monitor. Readings were noted over four components; Reactor, Cartridge, Waste vial and Product vial. The survey meter was placed on the shielded lid above the reactor and the cartridge for the reactor and cartridge readings, respectively. Similarly separate readings were taken for the waste vial and the product vial by placing the survey meter on a stand in front of the respective vials.
Readings were taken at each of the following steps:
Results: The pattern of the observed readings were recorded. For waste readings ranging from 1-20 mR /Hr the corresponding waste activity range was 0.15 - 2.43 mCi. For product readings ranging from 40-50 mR/Hr the corresponding product range activity was 6.2-12 mCi. (See table). Conclusion: The use of a survey meter to trace the path of the Ga 68 labeled product in the shielded IQS Ga 68 Fluidic Labeling module by ITG, helped to optimize the procedure by allowing troubleshooting before the end of the procedure & by giving a rough estimate of the final available activity.
- Introduction of Ga 68 in the reactor.
- Transfer of the labeled product to the cartridge with collection of unlabelled product in the waste vial.
- Elution with ethanol and rinsing with saline of the cartridge with collection of the labeled product in the product vial.
Neutron Activated 45 CaCl 2 for Metastatic Bone Pain Palliation: A Cost Effective Alternative to 89 SrCl 2 ?
Ramu Ram, 1 Rubel Chakravarty, 1,* Sudipta Chakraborty, 1 K. V. Vimalnath Nair, 1 A. Rajeswari, 1 H. D. Sarma 2 and Ashutosh Dash 1
1 Isotope Production and Applications Division, 2 Radiation Biology and Health Sciences Division, Bhabha Atomic Research Centre, Trombay, Mumbai - 400 085, India
Background and Aim: With an objective to develop a cost-effective bone pain palliation agent, we have demonstrated a viable method for large-scale production of 45 Ca (t = 163 d, E bmax = 0.3 MeV) using moderate flux research reactor, its purification from radionuclidic impurities adopting solvent extraction approach and preclinical utilization as 45 CaCl 2 . Materials and Methods: Irradiation parameters were optimized by theoretical calculations for large-scale production of 45 CaCl 2 . The radioisotope was produced in reactor by irradiation of isotopically enriched (> 98 % in 44 Ca) CaO target at a thermal neutron flux of ~ 1 × 10 14 n.cm -2 .s -1 for 4 months. Scandium-46 impurity co-produced along with 45 Ca was efficiently removed by solvent extraction approach using tributyl phosphate in dodecane (30 % tributyl phosphate in dodecane) as extractant. The bone specificity of 45 CaCl 2 was established by in vitro studies involving its uptake in hydroxyapatite (HA) particles and also evaluating its biodistribution pattern over a period of 2 weeks after in vivo administration in Wistar rats. Results: Thermal neutron irradiation of 100 mg of 44 CaO target followed by radiochemical processing and solvent extraction based purification procedure yielded ~ 37 GBq of 45 Ca with a specific activity of ~370 GBq/g and radionuclidic purity > 99.99 %. The reliability and reproducibility of this approach was amply demonstrated by process demonstration in several batches. In vitro studies indicated significant uptake of 45 CaCl 2 (up to 65 %) in HA particles. In vivo biodistribution studies in Wistar rats showed specific skeletal accumulation (40-46 %ID/g) with good retention over a period of 2 weeks. Conclusions: To the best of our knowledge, this is the first study on utilization of 45 CaCl 2 in context of nuclear medicine. The results obtained in this study hold promise and warrants further investigations for future translation of 45 CaCl 2 to the clinics, thereby potentially enabling a cost-effective approach for metastatic bone palliation especially in developing countries.
Preparation of 99m Tc-'4+1' Mixed Ligand Complex of 2-Nitroimidazole as a Marker for Tumor Hypoxia
Kusum Vats 1 , Madhava B. Mallia 1 , Anupam Mathur 3 , Haladhar D. Sarma 2 ,Sharmila Banerjee 1 *
1 Radiopharmaceuticals Chemistry Section, 2 Radiation Biology and Health Science Division, Bhabha Atomic Research Centre, Trombay, Mumbai - 400 085, 3 Medical and Biological Products Program, Board of Radiation and Isotope Technology, Mumbai - 400 705, India
Background and Aim: The '4+1' route for the preparation of 99m Tc-complexes is relatively recent and less explored. The '4+1' mixed-ligand complexes consist of central Tc(III) metal coordinated to a tetradentate tripodal chelator 2,2′,2″-nitrilotriethanethiol (NS 3 ) and a monodentate isocyanide ligand. The '4+1' mixed ligand complexes are neutral and could be prepared in excellent yield under mild reaction conditions. Additionally, they exhibit high stability against ligand exchange in vivo. In the present work, isocyanide derivative of 2-nitroimidazole was synthesized and radiolabled with 99m Tc using '4+1' mixed ligand approach. Materials and Methods: The target compound 1-(3-isocyanopropyl)-2-nitro-1H-imidazole (2nimNC) was synthesized from 2-nitroimidazole following a three step synthetic procedure. 2-nitroimidazole was reacted with 3-(Boc-amino)propyl bromide in the presence of potassium carbonate in acetonitrile. The crude product was purified and subsequently treated with 2N HCl to remove Boc- group. The amine hydrochloride (3-(2-nitro-1H-imidazol-1-yl)propan-1-amine hydrochloride) thus obtained was converted to N-(3-(2-nitro-1H-imidazol-1-yl)propyl)formamide by refluxing with ethylformate and then to the target ligand 1-(3-isocyanopropyl)-2-nitro-1H-imidazole (2-nimNC). The 99m Tc mixed ligand complex [(2nimNC) 99m Tc(NS 3 )] was prepared in two steps. In the first step 99m Tc-EDTA complex was prepared and to this 2-nimNC (0.1 mg) and NS 3 (1 mg) was added. The reaction mixture was incubated at 100 °C for 30 min and the final complex obtained was characterized by HPLC. In vitro stability (human serum, 37 °C, 3 h) and biodistribution studies (fibrosarcoma tumor bearing Swiss mice; 1 h, 3 h; n = 3) were subsequently carried out. Results: The complex [(2nimNC) 99m Tc(NS 3 )] could be prepared in excellent yield (> 90%) as determined by HPLC. The complex was found to be stable in vitro in human serum. Preliminary biodistribution studies showed uptake in tumor (0.44 ± 0.1% IA/g) at 1 h p.i and about 70% of the tumor uptake was found to be retained in tumor even at 3 h p.i. Major clearance of the activity was through hepatobiliary route. The tumor/muscle ratio improved with time attaining a value of 3.26 at 3 h p.i. Conclusion: A2-nitroimidazole isocyanide derivative was synthesized and radiolabeled with 99m Tc via the '4+1' route. Preliminary biological evaluation in Swiss mice bearing fibrosarcoma tumor showed uptake and retention of this complex in tumor.
Preparation and preliminary bioevaluation of 68 Ga-labeled lipiodol as a potential radiotracer for hepatocellular carcinoma
Subhajit Ghosh 1 , Tapas Das 1 , Haladhar D. Sarma 2 , Sharmila Banerjee 1
1 Radiopharmaceuticals Chemistry Section, Radiochemistry and Isotope Group, 2 Radiation Biology and Health Sciences Division, Bhabha Atomic Research Centre, Trombay, Mumbai - 400 085, India
Background and Aim: Lipiodol, an iodinated and esterified lipid of poppy seed oil, functions as an embolizing agent for trans-arterial embolization and is used to deliver localized doses of chemotherapeutic drugs as well as ionizing radiation to cancerous tissue of the liver. Therefore, an attempt has been made to prepare 68 Ga-labeled lipiodol, which may have potential as a PET radiotracer for imaging of hepatocellular carcinoma. Materials and Methods: Gallium-68-labeled lipiodol was prepared following a two-step procedure involving preparation of highly lipophilic 68 Ga-labeled oxine (8-hydroxyquinoline) complex followed by its subsequent extraction in lipiodol. 68 Ga was obtained from a 68 Ge- 68 Ga generator which was eluted with 0.1 N HCl (5 mL) and subsequently concentrated (250 µL) prior to actual preparation. 68 Ga-labeled oxine complex was prepared by incubating a mixture of ethanolic solution of oxine (100 µL, 1 mg) with 68 Ga (~37 MBq) in presence of NH 4 OAc-AcOH buffer (pH=5) at 100 ΊC for 45 min. Various reaction parameters such as, ligand (oxine) concentration, incubation time and temperature were varied in order to arrive at the optimized radiolabeling protocol. Radiochemical purity of the 68 Ga-oxine complex was determined by solvent extraction technique using CHCl 3 . For the dispersion of 68 Ga-oxine complex in lipiodol, the complex was extracted inCHCl 3 and the organic layer was evaporated to near-dryness by gentle heating. Lipiodol (500 µL) was added to the residue of 68 Ga-oxine complex and the reaction mixture was incubated at 60 ΊC with occasional stirring for 30 min. The stability of 68 Ga-lipiodol preparation, thus obtained, was studied by incubating the preparation with normal saline at room temperature and determining the 68 Ga activity leaching out into the aqueous layer at different time intervals, post-preparation. Preliminary biological evaluation of the agent was carried out by biodistribution studies using normal Wistar rats. The preparation was administered through hepatic artery and activity retained in the liver was determined at various post-administration time-points. Results: Gallium-68-labeled oxine complex was prepared with >95% radiochemical purity under optimized radiolabeling conditions. It was found that >90% of the 68 Ga activity could be dispersed in lipiodol medium. The radiolabeled preparation was found to exhibit good stability in physiological saline up to 3 h. The biodistribution study revealed satisfactory hepatic retention with insignificant uptake in any other major organ/tissue till 2 h post-injection, up to which the study was continued. Conclusion: Gallium-68-labeled lipiodol preparation exhibited promising potential for evaluation as a PET radiotracer for imaging of hepatocellular carcinoma and warrants further investigation.
Preparation and bioevaluation of [ 99m TcN] 2+ -labeled tetrameric complex of E-[c(RGDfK)] 2 as a radiotracer for targeting α v ß 3 integrin over-expression in tumors
Mohini Guleria 1 , Subhajit Ghosh 1 , Tapas Das 1 , Haladhar D. Sarma 2 , Sharmila Banerjee 1
1 Radiopharmaceuticals Chemistry Section, Radiochemistry and Isotope Group, 2 Radiation Biology and Health Sciences Division, Bhabha Atomic Research Centre, Trombay, Mumbai - 400 085, India
Background and Aim: Radiolabeled Arg-Gly-Asp (RGD) peptide is reported to have specific affinity towards α v ß 3 receptors of integrin family and therefore radiolabeled RGD peptide is considered as a potential agent for non-invasive imaging of tumors, over-expressing such receptors. The objective of the present work is to radiolabel a dimeric RGD peptide namely, E-[c(RGDfK)] 2 using [ 99m TcN] 2+ core in order to obtain a 99m Tc-labeled tetrameric RGD species, which is expected to have an enhanced tumor affinity. Materials and Methods: Technetium-99m-labeled tetrameric RGD species was prepared by the reaction between dithiocarbamate (DTC) derivative of E-[c(RGDfK)] 2 and preformed [ 99m TcN] +2 core.DTC derivative of E-[c(RGDfK)] 2 was synthesized by addition of a solution of carbon disulphide (0.5 mL) in ethanol to a pre-cooled solution of E-[c(RGDfK)] 2 (5 mg) in aqueous ammonia at 0 ΊC under constant stirring and subsequently incubating the reaction mixture overnight at room temperature. [ 99m TcN] +2 core was prepared by incubating a mixture of succinicdihydrazide (5 mg) and propylenediaminetetraacetic acid (5 mg) in 1 mL of phosphate buffered saline with Na 99m TcO 4 (~37 MBq) in presence of SnCl 2 .2H 2 O (50 µg) at room temperature for a period of 30 min. Formation of [ 99m TcN] +2 intermediate was ascertained by paper chromatography using normal saline and ethanol:chloroform:toluene:0.5 M ammonium acetate (6:3:3:0.5 v/v) as eluting solvents. In the subsequent step, 99m TcN-[E-c(RGDfK) 2 ] 2 was prepared by incubating freshly prepared [ 99m TcN] +2 intermediate (~15 MBq) with DTC derivative of E-[c(RGDfK)] 2 (25 µg) in saline for 1 h at 40 °C at pH ~5. Radiochemical purity of the 99m TcN-[E-c(RGDfK) 2 ] 2 was determined by HPLC using water and acetonitrile mixed with 0.1% trifluoroacetic acid as the mobile phase employing gradient elution technique.In-vitro stability of 99m TcN-[E-c(RGDfK) 2 ] 2 was studied by incubating the preparation in human serum at 37 °C up to 3 h. Pharmacokinetics and biological distribution of the 99m TcN-[E-c(RGDfK) 2 ] 2 complex were studied by carrying out biodistribution studies in C57BL/6 mice bearing melanoma tumors. Results: HPLC profile revealed that 99m TcN-[E-c(RGDfK) 2 ] 2 complex was prepared with high radiochemical purity (>95%) and adequate in-vitro stability under optimized radiolabeling conditions. Biodistribution studies revealed good tumor uptake within 30 min of administration (3.94±0.87 % IA/g) and retention therein till 2 h post-injection (2.65±0.31 % IA/g) up to which the study was continued. Blocking experiment carried out by co-administering excess of unlabeled peptide revealed the specificity of the complex towards the α v ß 3 receptors over-expression in the tumor model. Conclusion: Technetium-99m-labeled tetrameric RGD exhibited good specificity towards integrin a v ß 3 receptors over-expression and needs further investigation.
Preparation of 68 Ga-PSMA-HBED-CC for PET-CT imaging of Prostate cancer
Raviteja Nanabala, Arun Sasikumar, Ajith Joy and M.R.A. Pillai
DDNMRC PET Scans, Kerala Institute of Medical Sciences, Anayara PO, Trivandrum, India
Background and Aim: 68 Ga-PSMA-HBED-CC ( 68 Ga-PSMA) is a novel tracer used for PET imaging of prostate cancer patients. This paper presents our experience in the preparation of the radiopharmaceutical using the itG 68 Ge/ 68 Ga generator and the iQS fluidic system. Materials and Methods: 68 Ge/ 68 Ga generator and a semi-automated iQS fluidic system used in this study was from ItG, Germany. Radiolabelling ofPSMA-HBED-CC (M.W. = 947 Daltons) with 68 Ga (T 1/2 = 68 minutes, ß + =89%, ß max =1.9 MeV) was carried out as per a standard operating procedure supplied by the manufacturer. PSMA-HBED-CC ligand was dissolved in 1 ml of 0.25 M of Sodium acetate solution and mixed with 4 ml (15-27 mCi) of the generator eluent in 0.05 M of HCl in a preheated reactor kept at 105 o C. The pH of the reaction mixture was 4-4.5 and the reaction mixture was kept heated for 5 minutes. Purification of the product was done in a pre-conditioned C-18 SEP PAK. The product was eluted through a 0.22 micron filter with 1 ml 70% ethanol and 5 ml 0.9% saline. For calculating the radiochemical yields, activity in the product, waste, filter and cartridge were measured in a dose calibrator. Patient studies were carried out using 3-4.5 mCi of the activity having 1.5-3 nmol of the peptide. Results: The complexation between the ligand and no carrier added (NCA) 68 Ga is very fast and can be achieved with relatively low concentration of the ligand in a short time period. Studies with varying peptide concentrations showed that high labelling yields could be obtained by using 1-10 nM of the ligand. Radiochemical yields achieved were >90% in all batches. Activity in the waste and cartridge were low in all batches, 2.0±1.3% and 2.32±1.05%, respectively. The RC purity of the product was high as all impurities were removed during purification. C-18 cartridge purification also helps in the elimination of 68 Ge 2+ breakthrough, if any, in final product which was confirmed by undetectable activity levels in product after 24 hours decay. The image quality was very good showing low non-target uptake and high SUVmax values for lesions. Conclusions: Radiolabelling of PSMA-HBED-CC using with 68 Ga showed reproducible radiochemical yields with low activity in the waste. The RC purity of the product was very high. More than 50 batches were done with no batch failure and the products were suitable for PET-CT imaging of prostate cancer.
In-house preparation of Macroaggregated Albumin (MAA) for 68 Ga labeling and its comparison with commercially available MAA
Akanksha Jain 1 , Suresh Subramanian 1 , Usha Pandey 1 , Haladhar Dev Sarma 2 , Ramu Ram 1 , Ashutosh Dash 1
1 Isotope Production and Applications Division, 2 Radiation Biology and Health Sciences Division, Bhabha Atomic Research Centre, Mumbai - 400 085, India
Background and Aim: 99m Tc labeled macroaggregated albumin (MAA) is routinely used for SPECT based lung perfusion scanning, to assess abnormalities in pulmonary blood flow. Owing to the superiority of PET over SPECT and the ease of availability of 68 Ga, a positron emitter, through a 68 Ge/ 68 Ga generator, we have attempted to prepare an indigenous kit of MAA for 68 Ga labeling and compared it with 68 Ga-MAA prepared using commercial MAA kits (cMAA). Biodistribution study and Cherenkov imaging was carried out in Swiss mice. Materials and Methods: In order to prepare MAA, 20 mg of human serum albumin was dissolved in saline to get a 20 % solution. An aqueous solution of stannous chloride was added to the HSA solution under inert atmosphere. The reaction mixture was diluted with 0.1 M phosphate buffer, Tween-80 was added and the reaction mixture was heated at 75°C for 10 min. It was cooled to room temperature. 500 µL each containing 1 mg of MAA and 250 µg of stannous chloride was dispersed into vials (with 5 % glucose as cryoprotectant), lyophilized and named as MAA 5 . Particle size distribution was done using optical microscope. Optimization of 68 Ga labeling with was carried out at different temperatures and pH conditions and serum stability was also determined. Biodistribution of 68 Ga-MAA 5 was carried out in Swiss mice at 15 min post-intravenous injection in comparison to commercial preparation ( 68 Ga-cMAA). Cherenkov imaging of 68 Ga-MAA 5 was also carried out in Swiss mice up to 1 h p.i. Results: The average particle size of MAA 5 (59.9±18.1 µm) was close to that of commercial MAA (52.9±15.2 µm). MAA 5 exhibited increasing radiolabeling yields with 68 Ga with increase in temperature.The best labeling yield (84.5±5.3 %) was obtained on incubation for 15 minutes at 75°C at pH 6. Retention of 68 Ga-MAA 5 in lungs of Swiss mice (71.6±2.1 %ID) was similar to that of 68 Ga-cMAA prepared using commercial kits (83.5±2.3 %ID). In vivo Cherenkov luminescent imaging of 68 Ga-MAA 5 in Swiss mice at 15 min and 60 min p.i. showed maximum retention of activity in lungs and negligible leaching into liver. Conclusions: An in-house optimized formulation of MAA for radiolabeling with 68 Ga was successfully prepared. The preparation showed comparable particle size, good 68 Ga labeling yield and in vitro stability to cMAA kits. In comparison to 68 Ga-cMAA, the in-house preparation showed similar pattern of in vivo distribution in Swiss mice with very good accumulation in lungs which was corroborated by Cherenkov Luminescent imaging.
Performance of itG 68 Ga/ 68 Ge generator: An institutional experience
Raviteja Nanabala, Arun Sasikumar, Ajith Joy, M.R.A. Pillai
KIMS-DDNMRC PET Scans, Anayara PO, Thiruvananthapuram, Kerala
Background and Aim: 68 Ga (T 1/2 68 min.) is a positron emitter formed the electron capture decay of 68 Ge (T 1/2 270 d). 68 Ga based PET-CT imaging is in demand due to the clinical utility of radiopharmaceuticals such as 68 Ga-DOTANOC for imaging neuroendocrine tumors (NETs); and 68 Ga-PSMA-HBED-CC for imaging prostate cancer. We present an analysis of the performance of the itG 68 Ge/ 68 Ga generator for five months. Materials and Methods: 68 Ge/ 68 Ga generator (28 mCi 68 Ge load) procured from iTG, Germany was used for this study. The generator was eluted with 4 ml of 0.05 M HCl and the elution efficiency was calculated based on the activity eluted and the decay corrected parent activity load in the generator. Fractionated elution was also performed with 0.5 ml eluent to determine the elution profile. 68 Ge breakthrough was estimated by measuring the radioactivity in the eluent after 36 hour decay. All activity measurements were done in a dose calibrator in the 68 Ga window. In order to carry out more than one synthesis per day, theoretical in growth curve of 68 Ga was generated and the activity eluted at time intervals as needed. Results : More than 94% of activity was eluted in 3 ml of elution; the maximum activity (>30%) being in the third fraction of elution. Trailing of activity was observed after 6 th fraction. The elution efficiency of the generator initially was >100% (probably due to higher activity load or calibration error of the dose calibrator). There was a slow and steady decline (>100% to ~86%) in the elution yield over a period of 5 months. No detectable activity was measured in the eluent after 36 hours of decay while using a dose calibrator indicating that the 68 Ge breakthrough was < 10 -5 %. The eluted solution showed detectable counts when measurement was done with a radiation survey meter, indicating that there is some breakthrough of 68 Ge; however, it gets eliminated in the purification step during synthesis. Over the 5 month period of study, 65 batches of 68 Ga-PSMA; 28 batches of 68 G-DOTANOC and 4 batches of 68 Ga-DOTA-TATE were prepared for clinical use. There was no batch failure. 116 elutions were done from the generator in a span of five months. Conclusion: The 68 Ge/ 68 Ga generator supplied by iTG showed performance as expected from a good quality generator. The elution profile is sharp; clinically useful radiopharmaceuticals could be prepared using the generator eluted 68 Ga and by using the standard operating procedure provided by the manufacturer.
Efficient synthesis of [ 18 F] fluoroethylraclopride for dopamine D2 receptors imaging using PET
Shefali Gola, Surbhi Prakash, Ambika Jaswal, Shubhra Chaturvedi, Nitin Kumar,
Puja Panwar Hazari*, Anil K. Mishra*
Division of Cyclotron and Radiopharmaceutical Sciences, INMAS, DRDO, Brig. S K Mazumdar Road, Timarpur, Delhi- 110054
Background and Aim: Positron Emission Tomography (PET) functional brain imaging has facilitated the diagnostics and therapeutic approaches for various neurological and neuropsychiatric disorders. [ 11 C]Raclopride is a standard PET radioligand for investigation of dopamine D2 receptor density, distribution and deficiency. However, the use of [ 11 C]Raclopride possess certain limitations like short half-life and low efficiency. These inadequacies have established the need to label raclopride with a radioisotope which could enhance its efficiency for imaging. Thus, with the aim of development of a more efficient and stable dopamine receptor binding radiotracer with longer half life, 18 F labeled fluoroethylraclopride has been synthesized. Materials and Methods: The radiochemical synthesis of [ 18 F]fluoroethylraclopride is accomplished via two steps. [ 18 F]fluoroalkyl tosylate is prepared by [ 18 F]fluoro substitution on ditosylate in the presence of an efficient phase-transfer catalyst Kryptofix 222. [ 18 F]fluoroalkyl tosylate is then allowed to alkylate a secondary amine precursor to yield [ 18 F]fluoroethylraclopride. Purification of the product is achieved in single step using HPLC. Results: The radiochemical yield of the final product is approximately 25% (decay corrected). Animal studies also demonstrated that the maximum uptake of [ 18 F]fluoroethylraclopride reached within 15 minutes post injection. Conclusion: [ 18 F]fluoroethylraclopride has displayed increased half-life, good brain uptake, high stability and specificity. It has proved to be a potential candidate for PET imaging of dopaminergic receptors.
Neutron Activated 64 CuCl 2 : A Cost-Effective Probe for PET Imaging of Cancer
Rubel Chakravarty, 1, * Sudipta Chakraborty, 1 K. V. Vimalnath, 1 Priyalata Shetty, 1 Haladhar Dev Sarma, 2 P. A. Hassan 3 and Ashutosh Dash 1, *
1 Isotope Production and Applications Division, 2 Radiation Biology and Health Sciences Division, 3 Chemistry Division, Bhabha Atomic Research Centre, Trombay, Mumbai - 400 085, India
Background and Aim: Copper-64 (t = 12.7 h., E.C. 45%, b - 37.1%, b + 17.9%) is a promising radionuclide for positron emission tomography (PET) imaging which is generally produced by 64 Ni (p, n) 64 Cu reaction in a cyclotron. Despite excellent attributes of 64 Cu for PET imaging, the utility of this radioisotope is still limited to countries having good cyclotron facilities and excellent production logistics. We have explored the feasibility of using 64 Cu in the form of 64 CuCl 2, produced in medium flux research reactors by (n, γ) route, as a probe for tumor imaging by PET. Materials and Methods: The irradiation parameters (neutron flux and irradiation time) for production of 64 CuCl 2 with adequate specific activity and radionuclidic purity for use as a PET radiotracer were optimized by theoretical calculations using standard Bateman equations. The practicality of the approach was demonstrated by production of this radioisotope in several batches in the Dhruva reactor of our research centre. Exploring copper metabolism as an imaging biomarker, 64 CuCl 2 can directly be used as an effective probe for non-invasive visualization of tumors. The stability of 64 CuCl 2 under physiological conditions was assessed by detailed in vitro studies in mouse serum medium. The biological efficacy of 64 CuCl 2 was studied in C57BL/6 mice bearing melanoma tumors and Swiss mice bearing fibrosarcoma tumors. Results: From theoretical calculations, it was demonstrated that it is essential to carry out the irradiation of 63 Cu at flux of ~1 × 10 14 n.cm -2 .s -1 for at least 2 days to produce 64 Cu with adequate specific activity and high radionuclidic purity. On irradiation of 13 - 22 mg of natural CuO target in the Dhruva reactor of our research centre, the activity of 64 Cu after radiochemical processing varied between 30 and 57 GBq (specific activity ~3 TBq/g), which is appreciably high for both preclinical as well as clinical studies. The results of the in vitro studies indicated that 64 CuCl 2 remained as 64 Cu 2+ ion when incubated in mouse serum medium at 37 °C over a period of 24 h. The results of the biodistribution studies revealed significant tumor uptake (7.64 ± 1.71 %ID/g in melanoma, 6.54 ± 1.41 %ID/g in fibrosarcoma) within 4 h post-injection of 64 CuCl 2 , with good tumor-to-background contrast.
Conclusions: Owing to availability of several medium-flux nuclear reactors with good geographical distribution in different parts of the world, the promising results obtained in this study would set the stage for wide-scale utilization of neutron activated 64 CuCl 2 as a cost-effective probe for PET imaging.
Development of a PET Radiopharmaceutical for Infection Imaging: 68 Ga-NODAGA-UBI (29-41)
Jyotsna Bhatt 1 , Aruna Korde 1 , Archana Mukherjee 1 , Mukesh Kumar 2 , Ashutosh Dash
1 Isotope Production and Application Division, 2Solid State Physics Division, Bhabha Atomic Research Centre, Mumbai - 400 085, India
Background and Aim: Peptides labeled with positron-emitting radionuclides for use in positron emission tomography (PET) imaging have gained significant attention owing to their ability to provide quantitative information about biological processes in vivo. Ubiquicidin (29-41 fragment) an antimicrobial peptide labeled with 99m Tc ( 99m Tc-UBI (29-41)) is reported as a promising SPECT agent for infection imaging. The aim of the present study is to label UBI (29-41) with 68 Ga and explore its potential as a PET radiopharmaceutical for specific imaging of infection. Materials and Methods: Conjugate NODAGA-UBI (29-41) was custom synthesized for 68 Ga labelling. Conjugate was compared with UBI (29-41)) for its biological function by determining minimum inhibitory concentration (MIC) in S. aureus ATCC25923 bacterial cells. Both conjugate and parent molecules were also compared for their conformational properties using CD spectroscopy. 68 Ga was eluted from commercial 68 Ge/ 68 Ga generator in 0.6 N HCl and used without post elution purification. Radiolabeling of NODAGA-UBI (29-41) was optimized by varying pH, temperature, time and concentration of NODAGA-UBI (29-41)conjugate. Typically ~ 55MBqof 68 Ga with 2 M sodium acetate (pH 4) was added to the vial containing 50·gNODAGA-UBI (29-41). Reaction was performed at 90·C for 15 minutes. Radiochemical purity (RCP) of 68 Ga NODAGA-UBI (29-41) was determined by HPLC. Studies on stability of the complex in saline and serum were also carried out. Uptake of radiolabelled NODAGA-UBI (29-41) conjugate was studied in-vitro in S. aureus ATCC25923 cells. Results: UBI (29-41) and NODAGA-UBI (29-41) showed MIC>150 micromolar for S. aureus ATCC25923cells. Both molecules share their conformational properties even at varying salt concentrations. Under optimized conditions, 68 Ga NODAGA-UBI (29-41) was prepared in high yields and purity (RCP >98%) as determined by HPLC. The complex eluted at R t of 14-15 min in gradient elution system with solvent system of Acetonitrile/H2O with 0.1TFA at a flow rate of 1ml/min. The complex was stable in saline and serum. Radiolabelled conjugate showed specific uptake in S. aureus ATCC25923 cells.
Conclusion: UBI (29-41) and NODAGA-UBI (29-41) show similar function and conformation under the tested conditions. Radiolabeling of NODAGA-UBI (29-41) with 68 Ga, characterization of complex and its in-vitro evaluation using S. aureus ATCC25923 was successfully carried out. Studies reveal 68 Ga NODAGA-UBI (29-41) to be a promising agent for preclinical evaluation for infection imaging.
Patient dose preparation of 131 I- LIPIODOL using GMP compliant synthesis module and its biological evaluation
Aruna Korde, Suresh Subramanian, R. N. Ambade, B. G. Avhad, Ashutosh Dash
Isotope Production and Applications Division, BARC, Mumbai, India
Background and Aim: Intra-arterial injection of 131 I Lipiodol delivers high radiation dose to hepatocellular carcinoma (HCC) with minimal accumulation in adjacent normal tissue. Hence it has become effective treatment modality for primary HCC, a highly morbid cancer with increasing incidence especially in the Asian region. GMP compliant radiosynthesis of 131 I Lipiodol suitable for patient dose preparation and its radiochemical, pharmaceutical & biological evaluation in laboratory animals is reported herewith. Materials and Methods : The synthesis module suitable for remotely carrying out radiosynthesis was fabricated. Synthesis was carried out using isotopic exchange reaction of Na 131 I with iodine of lipiodol. The procedures were standardized for labelling and operation protocol of synthesis module was set up to achieve optimal yield and purity. The module was installed with adequate shielding and a system of charcoal filters to trap released iodine. Scaling up of reaction was carried out and patient dose of up to 3.3 GBq 131 I-Lipiodol was prepared. Continuous area monitoring and radiation survey was carried out during dose escalation studies. The prepared product was evaluated for radiochemical purity using ITLC with 85% methanol. The biological evaluation was carried out by injecting the product in normal adult Wistar rats via portal vein (~7.4 MBq per animal) using surgical procedures. Biodistribution studies were carried out for 16 h, 1 day, 3 days and 5 days to determine dose retention in liver. Results : The fabricated module remotely enables precise liquid transfers and controlled heating leading to consistent yields of 45 to 50% when isotope exchange reaction was carried out. The dose escalation studies were safely carried out without measurable radioactive iodine release. The operation protocol allows safe and user friendly remote operation. The cleaning protocols and feasibility of filter sterilization of final product ensures pharmaceutical purity and safety of the product. The radiochemical purity of 131 I-Lipiodol was >95% as determined by ITLC. The product was stable for two weeks when stored in dark at ambient temperature. Bio-distribution studies revealed retention of injected product in liver without significant leakage of activity to other organs including thyroid. Conclusion : The GMP compliant indigenously designed and fabricated module is successfully applied for patient dose preparation of 131 I-Lipiodol. The pharmaceutically pure product was prepared in good yields and >95% purity with adequate in-vivo stability determined by animal biodistribution studies.
Biological evaluation of 99m Tc HYNICTATE prepared using formulated cold kit
Aruna Korde, H. D. Sarma,Jyotsna Bhatt, Ashutosh Dash
Isotope Production and Application Division, Bhabha Atomic Research Centre, India
Background and Aim : [ 99m Tc]HYNICTOC prepared using indigenous cold kits has become successful radiopharmaceutical for diagnostic imaging of tumors over-expressing somatostatin receptors. Different SSTR subtypes (1-5) are over-expressed in varying intensities in different types of tumors. Octreotate is known to have more affinity for SSTR2 subtype and preferred analogue for PRRT using radiolabeled peptides such as 177 LuDOTATATE. Hence 99m Tc labelled Octreotate based tracer will be more suitable for diagnosis, screening, radiotherapy planning and post therapy evolution of SSTR expressing tumors. We herein report kit based formulation for preparation of 99m Tc HYNICTATE and its radiochemical and biological evaluation in nude mice bearing human pancreatic tumor. Material and Methods : The peptide conjugated with HYNIC for complexation with 99m Tc was procured from Pichem. Single vial freeze dried kit formulation was developed. The kits were prepared under aseptic conditions and evaluated for pharmaceutical safety and purity by sterility and BET testing as per pharmacopeia procedures. Radiolabeling protocol for preparation of [ 99m Tc]HYNICTATE was optimized using 99m Tc eluted from in-house set up of 99 Mo- 99m Tc alumina column generator. HPLC analyses were performed using C18 reversed phase column (5·, 250x4 mm) and gradient solvent using Acetonitrile/H2O 1% TFA at a flow rate of 1 mL/min. The labeling efficiency, radiochemical purity and stability of lyophilized kit were studied using upto 2.2 Gbq of 99m TcO 4 - . MIAPaCa-2 Human pancreatic cells were cultured in-vitro in DMEM containing 10% FCS, 100 U/mL penicillin, 50 µg/mL streptomycin in humidified atmosphere under 5% CO 2 at 37°C. ~10 7 cells were injected in Nude mice subcutaneously in flank region. 99m Tc HYNICTATE was injected via tail vein in tumor bearing mice and bio-distribution studies were carried out to determine pharmacokinetics and tumor uptake. Results : Freeze dried kit formulation containing 30ug HYNICTATE, 10mg EDDA, 20mg Tricine 50µg SnCl 2 and buffer salts was found to be stable and sterile and pyrogen free. [ 99m Tc] HYNICTATE prepared using freeze dried formulation and upto 2.2GBq of 99m TcO 4 - resulted in desired purity (>90%) and stability. Biodistribution studies carried out in nude mice bearing MIAPaCa-2 tumors exhibited tracer uptake of 5.21±0.6 % ID/gm of tumor tissue which was significantly inhibited by prior injection of higher concentration of octreotate indicating in-vivo specificity for SSTR. Conclusion: A freeze dried cold kit formulation suitable for convenient radiolabeling of [ 99m Tc]HYNICTATE was prepared and evaluated for receptor specificity, purity and stability.
Design, molecular modeling, synthesis and bio-evaluation of [ 11 C]BTZ-MPP based mixed affinity radioligand: A novel PET neuroimaging agent for 5-HT 1A and 5-HT 7 receptors
Preeti Jha 1, 2 , Swastika Mishra 1, 3 , Shubhra Chaturvedi 1 , Nidhi Jain 2 and Anil K Mishra 1*
1 Division of Cyclotron and radiopharmaceutical Sciences, INMAS, DRDO, Timarpur, Delhi - 110 054, 2 Department of Chemistry, Indian Institute of Technology, Hauz Khas, Delhi - 110 016, 3 Department of Chemistry, Banaras Hindu University, Varanasi, U.P.-221005.
Background and Aim: The GPCRs, 5HT 1A and 5HT 7 are known to co-exist as dimers in the CNS and have been implicated in depression, anxiety and mood regulation. Imaging of these receptors is important to assess the quantitative and functional aspect of neurological disorders. In the present work, we aimed to modify MPP (2-Methoxyphenylpiperazine) skeleton with BTZ (benzothiazolone) moiety and developed a novel radioligand, BTZ-MPP (3-(3-((2-(4-(2-methoxyphenyl)piperazin-1-yl)ethyl)amino)propyl)benzo[d]thiazol 2(3H)-one) for targeted [ 11 C]-PET neuroimaging of 5-HT 1A/7 Rs. Materials and Methods: Ligand was designed on the basis of ADME and physicochemical parameters established using Qikprop. The 3D-structures of 5HT 1A/7 Rs were generated using Homology Modeling, Schrφdinger's Software. The 3D-quality of models were validated through Ramachandran Plot, Ligand docking and MD simulations. Synthesis involves the conjugation of 1-Bromo-3-chloropropane with BTZ (m/z = 227), and N-BOC-bromoethylamine (m/z = 223) with MPP to yield MPP-N-BOC-bromoethylamine (m/z = 335). The BOC group was de-protection with TFA/DCM into MPP-NH 2 (m/z = 235) in 90% yield. Resulting primary amine then conjugated with BTZ-Cl in the presence of base yields 80% secondary amine compound (m/z = 427) using SN 2 reaction mechanism. The compound and intermediates were characterized by 1 H, 13 C and MASS spectrometry. Compound was then cold labeled with CH 3 I in 95% yield and radiolabeled with [ 11 C] with labeling efficiency of 95-99%. MTT assay was performed to assess the cellular toxicity. PET imaging and biodistribution studies are in progress. Results: [ 11 C]BTZ-MPP was designed, synthesized and validated theoretically using molecular modeling studies. Receptor ligand interaction studies via docking analysis reveals the presence of Asp162, Val163, Leu370, Arg367, Phe343, Phe344, Arg350 and Asp116, Ile189, Lys191, Ser199, Thr200, Phe361, Phe362 amino acid residues in the active binding site pocket of 5HT 7 and5-HT 1A Rs. The values oflogPo/w, logBB and logS were calculated to be 3.9, 0.35 and -3.85, ensuring drug likeliness of synthesized compound. The XP GScore of BTZ-MPP for monomeric 5-HT 1A , 5-HT 7 , homodimeric 5-HT 1A -5-HT 1A , 5-HT 7 -5-HT 7 andheterodimeric5-HT 1A -5-HT 7 Rs were found to be -8.587, -7.063, -11.151, -8.816 and -9.0 respectively, whereas -7.684, -11.517 and -3.241, -7.242 were obtained for mono- and homodimeric forms of 5-HT 1A and 5-HT 7 Rs for native ligands 5-HT (5-HT 1A ) and SB-269970 (5-HT 7 ), indicating a better binding affinity, selectivity and specificity of the synthesized ligand. MTT assay showed no significant toxicity at low nanomolar concentrations. Conclusion: Feasible synthesis of novel [ 11 C]BTZ-MPP radioligand along with physicochemical characterization has been manifested, having a strong potential application as 11 C-radiopharmaceutical for neuronal PET imaging.
Nucleolipid Derivatised Monoamide Dtpa: Synthesis Based On Molecular Weight Cutoff Cassette and Preliminary Evaluation For Spect Imaging
Swastika Mishra, Preeti Jha, Shubhra Chaturvedi, Ankur kaul, B. Singh and Anil Kumar Mishra*
Division of Cyclotron and Radiopharmaceutical Sciences, Institute of Nuclear Medicine and Allied Sciences, Brig. S. K. Mazumdar Road, Delhi - 110 054, India
Background and Aim: Nuclear Imaging is important for determining the stage and the precise locations of disease for example cancer in order to aid in directing surgery and treatment planning. Nucleoside analogs have therapeutic applications as anticancer and antiviral drugs because of their immense biological and clinical importance, efficient entry of nucleosides and their analogs into the cell is crucial to human health and disease. However, nucleolipids are often restricted by a poor stability in vivo, and limited passive intracellular diffusion due to their hydrophilicity. Site-specific bioconjugation enables to protect sensitive groups from enzymatic degradation and the coupling of hydrophobic moieties may yield amphiphilic conjugates able to cross the plasma membrane by passive diffusion namely BBB. In the present work we describe the synthesis and biological evaluation of DTPA functionalized ketal based nucleolipid. The ketal linkage is of pharmacological interest, as can be catabolized in a slightly acidic medium. This presents potential drugs for acidic tumors. Materials and Methods: The synthesis involves conjugation of 16-hentriacontanone at 2', 3' position of the ribose ring of uridine through ketal linkage. The 5' position was then converted into azide followed by reduction into primary amine using 10% Palladium as a catalyst. Resulting primary amine then conjugated to DTPA anhydride in the presence of base yields 80% monoamide compound. The compound and intermediates are characterised by 1 H, 13 C, and mass spectrometry. The ligand has also been radiolabelled with technetium and radiolabeling studies shows 98% radiolabelling efficiency using stannous tartarate at neutral PH. Biodistribution studies over different time-points shows regional brain uptake and hepatobiliary mode of excretion is seen predominantly. Qikprop properties for the ligand have been established using Schrφdinger's software. Cytotoxicity studies using the standard MTT assay have been performed. Results: The ketal conjugation of 16-hentriacontanone with uridine was achieved in more than 85% yield. DTPA catalyzed conjugate yields 85% . The lipidic chains appeared between 1.8 to 1.0ppm and the DTPA protons for the same between 3 to 4.6ppm. The m/z for final compound observed at 1050. The cytotoxicity studies using HEK cell lines indicate no appreciable toxicity up to 72h. Conclusion: Feasible synthesis of the ligand along with physico-chemical characterization has been demonstrated. The present study attempts the utility of nucleolipid as brain imaging agents.
Synthesis and its Pharmacological evaluation of 2-(2-(4-fluorophenyl)imidazo [1,2-a]pyridin-6-yl)oxazolo [4,5-b]pyridine (FPIPOP) as a novel PET imaging agent for ß-Amyloid
Shivani Singh a,b , Sweta Singh a , R. K. Sharma b and Anil. K. Mishra a
a Division of Cyclotron and Radiopharmaceutical Sciences, Institute of Nuclear Medicine and Allied Sciences, Brig. S.K. Mazumdar Road, New Delhi - 110 054, b Department of Chemistry, University of Delhi, New Delhi - 110 007, India
Background and Aim: Alzheimer's disease (AD), an irreversible, progressive neurodegenerative disorder, is clinically characterized by cognitive decline and synaptic loss. Two of the characteristic features of AD are the formation of extracellular deposition of ß-amyloid in the form of senile plaques (SPs), intracellular neuro-fibrillary tangles (NFTs) and neuronal cell death, but formation of SPs is considered an initial manifestation of AD. Thus, effort has been engrossed on the evolution of non-invasive biomarkers of SPs to diagnose and stage the disease. Hence, we have synthesized 2-(2-(4-fluorophenyl)imidazo [1,2-a]pyridin-6-yl)oxazolo [4,5-b]pyridine (FPIPOP) for PET imaging in brain. Materials and Methods : Firstly, 2-amino-3-hydroxypyridine is condensed with 6-aminonicotinic acid using polyphosphoric acid to give an oxazolopyridine with high purity. The resultant oxazole is conjugated with 4-nitrophenacylbromide to incorporate a position for 18-F labelling. This results in the formation of 2-(2-(4-nitrophenyl)imidazo [1,2-a]pyridin-6-yl)oxazolo [4,5-b]pyridine with good yield (80%). This nitro precursor is then radiolabelled with 18-F using K 18 F, and kryptofix. Thus we have developed a novel 18-F based prospective Aß imaging agent. Results: The synthesized ligand has been characterized successfully by different spectroscopic technique (NMR and Mass). Radiolabeling was achieved above 97% and radio conjugate is stable for 24hours in human serum and get dissociated less than 0.5%. The biological studies are under progress. The overall synthesis time, from EOB to HPLC analysis of 2-(2-(4-fluoro- 18 F-phenyl)imidazo [1,2-a]pyridin-6-yl)oxazolo [4,5-b]pyridine ( 18 F-FPIPOP)was 40 min and the retention time was found to be 5.2 min radiolabelled analogue. Specific activity was 122-174 GBq/mmol. Radiochemical purity determined by analytical Radio-HPLC was higher than 98%. Cytotoxity was determined by MTT assay. Conclusion: We were successful in synthesizing 2-(2-(4-fluorophenyl)imidazo [1,2-a]pyridin-6-yl)oxazolo [4,5-b]pyridine (FPIPOP). The biological evaluation is under process.
Batch Preparation and Quality Control of DOTA-TOC kits for preparation of 68 Ga-DOTA-TOC towards PET imaging of neuroendocrine tumors
Usha Pandey 1 , Archana Mukherjee 1 , Aruna Korde 1 , Haladhar Dev Sarma 2 , Ashutosh Dash 1
1 Isotope Production and Applications Division, 2 Radiation Biology and Health Sciences Division Bhabha Atomic Research Centre Trombay, Mumbai - 400 085.
Background and Aim: Gallium-68 labeled somatostatin receptor-avid peptides such as DOTA-TOC and DOTA-NOC have established themselves for PET imaging of neuroendocrine tumors due to high sensitivity and resolution of PET. Presently, 68 Ga-DOTA-TOC is synthesized using commercially available automated modules which are expensive. In the recent past, we had developed kit formulation of DOTA-TOC for facile 68 Ga labeling. Herein, batch preparation of DOTA-TOC kits and their quality control evaluation for preparation of 68 Ga-DOTA-TOC commensurate with regulatory requirements is reported. Materials and Methods: Towards batch preparation of DOTA-TOC kits, reagent concentrations and production procedures were standardized for a batch size of 20 vials. A typical batch preparation consisted of preparation of a stock solution consisting of 1 mL of DOTA-TOC solution (1 mg) and appropriate volume of 0.5 M sodium acetate solution which was then filtered, dispensed equally into twenty numbers of sterile glass vials so that each kit vial contained 50 µg of the peptide, lyophilized and vacuum sealed aseptically. The kits were subjected to tests for sterility and apyrogenicity. Thereafter, 68 Ga labeling was carried out by reconstitution of one kit vial with 0.2 mL of sterile HPLC grade water followed by the addition of 68 Ga activity (37-370 MBq) from a commercial generator in 1 mL of 0.1 N HCl, incubation at 90°C for 10 minutes followed by 20 µl of 4 mM EDTA and 6 mL of sterile saline resulting in ready-to-use 68 Ga-DOTATOC. Radiochemical purity was determined by HPLC and paper chromatography methods. In vitro stability in saline and serum was determined. Biodistribution studies were carried out in Wistar rats at 1 h post intravenous injection. Results: Six batches of DOTA-TOC kits were prepared and detailed quality control analysis of all batches was carried out. Each batch consisted of 20 DOTA-TOC kit vials with 50 µg of peptide per kit vial. Kits from all the batches passed sterility and apyrogenicity tests. > 90 % radiolabeling yields could be obtained on 68 Ga labeling (37- 370 MBq). 68 Ga-DOTA-TOC showed excellent in vitro stability in saline and serum up to 3 h post preparation. Shelf life of the formulated kits was determined to be eight months. Biodistribution in Wistar rats showed that 51.7±3.7 % of 68 Ga-DOTA-TOC was renally excreted 1 h p.i. without significant retention in vital organs. Specificity to somatostatin receptors was evident from the pancreatic uptake (3.7±0.3 %). Conclusion: Batch preparation of DOTA-TOC kits for preparation of 68 Ga-DOTA-TOC, commensurate with regulatory requirements, could be accomplished.
Synthesis and Biological Evaluation of ATRIDAT conjugated methionine based derivative for PET Imaging
Surbhi Prakash 1, 2 , Ambika Jaswal 1 , Virendra Meena 1, 2 , Harleen Khurana 1 , Ankita Pandey 1 , Anil K Mishra 1 and Puja P. Hazari 1
1 Institute of Nuclear Medicine and Allied Sciences, Delhi, 2 Delhi University, Delhi, India
Background and Aim: Amino Acid transporters are highly expressed in malignant tissue, involved mainly in the transport of amino acids to support continuous growth and proliferation of the abnormal tissue across endothelial and epithelial barriers. Methionine is specifically transported through LAT1 which was conjugated to an indigenously synthesized C-functionalized dioxodiacetate macrocyclic system (ATRIDAT) for M 2+ and M 3+ radiometals. The amino acid conjugate was designed to obtain signal at the target site for high resolution PET scans with 68 Ga. Methods: Boc-protected diethyl amino malonate was conjugated with triethylenetetramine in anhydrous methanol to get boc-protected macrocyclized product, namely tert-butyl (11,13-dioxo-1, 4, 7, 10-tetraazacyclotridecan-12-yl) carbamate. On further reaction with tert-butylbromoacetate and trifluoroacetic acid, ATRIDAT (2,2'-(12-amino-11,13-dioxo-1, 4, 7, 10-tetraazacyclotridecane-4,7-diyl)diacetic acid) was obtained. Further conjugation with methionine was carried out using NHS/DCC. 68 Ga- radiolabeling was performed at pH~4 and 90°C. Results: All intermediates and final compound have been fully characterized by spectroscopic techniques, namely, 1 H, 13 C NMR and mass spectroscopy. MET- ATRIDAT was obtained in appreciable yield (>71%) from condensation of boc-protected amino diethyl ester and triethylenetetramine. More than 70% 68 Ga-radiolabeling efficiency was obtained and the radioconjugate exhibited sufficient stability under physiological condition. Conclusion: Anew chelate incorporating methionine has been synthesized for PET imaging. The conjugate displays considerable thermodynamic and kinetic stability in vivo. Significant radiolabeling yield and uptake at the tumor site show its capability as a potential imaging agent.
Development of Tyrosine based SPECT imaging agent: Synthesis, characterization and in vitro Results
Priyanka Bhatngar, Shefali Gola, Puja Panwar Hazari and Anil Kumar Mishra*
Division of Cyclotron and Radiopharmaceutical Sciences, INMAS, DRDO, Brig. S. K. Mazumdar Road, Timarpur, Delhi - 110 054, India
Background: Amino acid uptake is generally increased in rapidly growing tumor cells when compared with normal cells. The higher accumulation of amino acids in cancer cells is strongly correlated with the expression of L- type amino acid transporter 1, which is upregulated in various malignant tumors of brain, colon, lung, liver, thymus, ovary, and skin. Therefore, many natural amino acids and their synthetic analogues have been labeled with radioactive isotopes and are being explored as tumor imaging agents for PET/SPECT. Diethylenetriaminepentacetic acid (DTPA), an effective chelating agent known to form stable complexes with various radionuclides, its derivatives with several amino acids have been successfully used as a target-specific radio-pharmaceutical. In the present investigation, tyrosine based DTPA conjugates were formulated to be used as an effective SPECT imaging agents. Materials and Methods: DTPA is covalently conjugated to tyrosine via formation of amide bonds. DTPA anhydride (500 mg; 1.4 mmol) and L-tyrosine (634 mg; 3.50 mmol) were dissolved in 5 mL of DMF (anhyd.), and 15 mol equiv of triethylamine (2.35 mL), was allowed to stir for 48 h at 55±2°C. The synthesized DTPA-tyrosine conjugate was characterized by 1 H-NMR, IR, Mass spectroscopy. The DTPA-tyrosine conjugate was labeled with 99m Tc by direct labeling method. 99m Tc-DTPA-tyrosine complex was evaluated for labeling efficiency followed by in vitro analysis. Results: The 1 H-NMR, IR, Mass spectra revealed the successful formation of the DTPA-tyrosine conjugate. 99m Tc-DTPA-tyrosine complex had an appreciable labeling efficiency of greater than 98%. The radiolabeled complex was found to be stable in in vitro conditions. Cellular uptake study in human tumor glioma cells (BMG and U87MG) demonstrated the higher intracellular uptake of the 99m Tc-DTPA-tyrosine complex as compared to 99m Tc-DTPA complex. Conclusion: It is evident from the in vitro analysis that the formulated 99m Tc-DTPA-tyrosine complex promises to be a potential tumor imaging agent.
Clinical Grade Automated Synthesis of Fluorodeoxyglucose [ 18 F] FDG at Newly Established Cyclotron Facility at SGPGIMS, Lucknow
Manish Dixit, Priya Saxena, Srishti Verma, Sarita Kumari, Subhash Kheruka, R. S Verma, Sanjay Gambhir
1 Department of Nuclear Medicine, Sanjay Gandhi Post Graduate Institute of Medical Sciences, Lucknow, India
Background and Aim: Fluorodeoxyglucose [ 18 F] FDG or FDG is a radiopharmaceutical used in the medical imaging modality positron emission tomography (PET). In PET imaging, 18 F-FDG can be used for the assessment of glucose metabolism in the heart, lungs and brain. It is also used for imaging tumors in oncology. FDG-PET can be used for diagnosis, staging, and monitoring treatment of cancers, particularly in Hodgkin's disease, non-Hodgkin's lymphoma, colorectal cancer, breast cancer, melanoma, and lung cancer. It has also been approved for use in diagnosing Alzheimer's disease. Materials and Methods : Routine and robust production of clinical grade [ 18 F]-FDG is outmost need of PET center. I this way in our newly established PET Cyclotron Facility, we are producing the clinical grade [ 18 F]-FDG using automated synthesizer (Sumitomo's FDG synthesizer F300E). Our cyclotron facility having Sumitomo Heavy Industries HM-18 cyclotron used for the routine production of various radioisotopes such as 18 F, 11 C, 13 N, 15 O, 64 Cu, and 124 I.[ 18 F]-Fluoride in 97%-enriched 18 O water was produced by an 18 O (p,n) 18 F nuclear reaction, using an 18.5 MeV HM-18 cyclotron. [ 18 F]Fluoride ion in 2.5 mL of water was trapped on a QMA cartridge and the trapped 18 F on QMA cartridge was eluted using K222/K 2 CO 3 and transferred into reaction vial. Subsequently, azeotropic drying using anhydrous acetonitrile and subsequent reaction with mannose triflate followed by base hydrolysis affords the crude product. The final reaction mixture was purified by passing through refining columns and pure product ([ 18 F]-FDG) was collected into dispensing sterile vial. The clinical grade purity of final product was performed using battery of tests. Results : - The overall uncorrected radiochemical yield was 55±2% with radiochemical purity more than 97%. Total synthesis time was 25 minutes. Conclusion : The clinical grade [ 18 F]-FDG production in our newly established cyclotron facility with high reproducibility and consistent yield was established. Details of the automated synthesis techniques along with quality control testing results of the product will be presented.
Technological Considerations for In-House Preparation of Lutetium -177 DOTA TATE Therapy of Neuroendocrine Tumours
Jennifer Kerenhappuch .R, Shelley Simon, Indirani .M, Jaykanth
Department of Nuclear Medicine, Apollo Hospitals, Chennai, India
Aim: Technological consideration and quality control for preparation of 177Lu labeled DOTA-TATE, for the treatment of somatostatin expressing inoperable neuroendocrine tumors. Materials and Methods: 177Lutetium chloride, DOTA-TATE peptide, boiling water bath that can attain 100 degree centigrade, 0.9 % NaCl. C-18 cartridge, 95% ethanol, one vacuum vial, one 5 ml syringe and 0.2 micrometer filter 177Lu labeling with DOTA-TATE is done using a pre-calculated amount of DOTA-TATE ensuring highestpossible specific activity of 177Lu -DOTA-TATE without compromising its radiochemical purity and stability. Post labeling quality control can be done by the following methods: Solid phase separation using SepPak C-18 cartridges, thin layer chromatography, paper chromatography, and high performance liquid chromatography. Post therapy scan should be done using medium energy collimator with dual energy window113 KeV [6.4% abundance] and 208 KeV [11% abundance]. Result: By following a standardized in-house protocol for 177Lu labeling, a labeling efficiency of more the 90 percent can be achieved and hence the target to back ground ratio is excellent in the post therapy scan. Poor labeling leads to bone uptake and ultimately leads to bone marrow suppression with unintended radiation exposure to normal tissues. Conclusion: Nuclear medicine technologist has an important role in house preparation of 177Lu labeled DOTA-TATE with desired labeling efficiency and highest possible specific activity. Post therapy scan ensures adequate quality control and desired distribution of radiopharmaceutical.
Clinical Grade Production of [ 13 N]-NH 3 by newly established 18.5 MeV Cyclotron SGPGIMS, Lucknow
Priya Saxena 1 , Manish Dixit 1 , Sarita Kumari 1 , Subhash Kheruka 1 , Sanjay Gambhir 1
1 Department of Nuclear Medicine, Sanjay Gandhi Post Graduate Institute of Medical Sciences, Lucknow, India
Background and Aim: [ 13 N]Ammonia ([ 13 N]NH 3 ) is a useful 13 N-labeled compound that has been developed as a positron emission tomography (PET) imaging agent for assessing regional blood flow in tissues, imaging of the myocardium under rest or pharmacologic stress conditions to evaluate myocardial perfusion in patients with suspected or existing coronary artery disease. [ 13 N]Ammonia is considered a safe and effective radiopharmaceutical and was approved by US FDA for PET imaging. Method: In our newly established cyclotron facility having Sumitomo Heavy Industries HM-18 cyclotron, has production facility of variety of radioisotopes such as N-13, F-18, I-124, Cu-64 and C-11. In order to produce clinical grade 13N]-NH 3 we use to load [ 16 O] H 2 O+ 5.0 mmol/L ethanol to target and it was bombarded to generate [ 13 N] enriched water by the 16 O (p, α) 13 N nuclear reaction. The radioactive 13 N was transferred to the automated synthesizer (Sumitomo's FCNO multipurpose synthesizing unit) having ammonia synthesis tray. The crude product was passed through Waters CM cartridge and the trapped product was further eluted with 0.9% saline to get the ammoniated water as [ 13 N]-NH 3 . Results: The overall radiochemical purity more than 99% with excellent yield . Conclusion: This new automated procedure allows [ 13 N]-NH 3 synthesis with high reproducibility that is essential for future clinical application. Details of the automated synthesis techniques along with quality control testing results of the product will be presented.
Analysis of Using Surgical Spirit as a Solvent in Chromatography
Abin M, Dayana S. J. Sibi O, Vasumathi, Rajesh K.
Department of Nuclear Medicine, School of Allied Health Science, Manipal University, Manipal - 576 104, Karnataka, India
Background: Acetone is a colourless solvent belongs to the ketone group. Its molecular weight is 58.08g.mol, boiling point is 56.29 degree centigrade and the freezing point is 94.7 degree centigrade. Acetone a stable product is a polar solvent constituting of 80% methanol, 2-butanone.Surgical spirit is a colourless, volatile, flammable, polar solvent with noxious smell. Its freezing point is 89 degree centigrade and is normally stable. It is prepared from a special denatured alcohol solution and contains approximately 70 % by volume of pure concentrated ethanol or isopropyl alcohol.Since surgical spirit or denatured alcohol is most commonly used in the hospitals and other medical facilities this study is aimed to check the efficacy of surgical spirit or denatured alcohol as a solvent to acetone in ascending paper chromatography to determine radiochemical purity of a radiopharmaceutical. Aim: To analyse surgical spirit as a solvent in ascending paper chromatography. Materials and Methods: Whatman paper , Test tubes, acetone (58.08g/mol) , saline( 0.9gm sodium chloride) ,surgical spirit , dose calibrator, radiopharmaceutical, GM counter, gamma ray spectrometer, standard sources. The radiopharmaceutical opted in this study is 99mTc - MDP. Using the solvents acetone, denatured alcohol, saline and radiation detection instruments GM counter, dose calibrator, gamma ray spectrometer the free, reduced hydrolysed technetium and bound fractions in 99mTc-MDP were determined. Result: Results obtained from surgical spirit and acetone is similar. Mean difference found for GM counter is 0.44± 1.15, dose calibrator 1.0± 2.6 and gamma ray spectrometer is 0.44± 1.15 range. Conclusion: Since error difference is less surgical spirit can be used instead of acetone as a solvent in ascending paper chromatography for RCP determination of 99mTc -MDP.
Development of a lyophilized single-vial kit for preparation of 188 Re(V)-DMSA at room temperature
Viju Chirayil, Madhava B Mallia, Sharmila Banerjee
Radiopharmaceuticals Chemistry Section, Radiochemistry and Isotope Group, Bhabha Atomic Research Centre, Trombay, Mumbai - 400 085, India
Background and Aim : 188 Re(V)-Dimercaptosuccinicacid (DMSA) is a therapeutic radiopharmaceutical for treatment of medullary carcinoma of thyroid as well as some soft tissue tumours. Present work describes the development of a single-vial kit for the preparation of 188 Re(V)-DMSA at room temperature using 188 Re obtained from a 188 W- 188 Re generator. Materials and Methods: Rhenium-188 activity in the form of Na 188 ReO 4 was obtained from 188 W/ 188 Re generator (Polatom). Meso-DMSA, L-ascorbic acid, sodium oxalate were purchased from M/s. Sigma-Aldrich, USA. To prepare a batch of 10 lyophilized kits, 22 mg DMSA, 55 mg of ascorbic acid and 55 mg sodium oxalate were dissolved in 4.5 mL of 53 mM sodium bicarbonate solution. To this, 4.4 mg of SnCl 2 .2H 2 O dissolved in 1 mL of 1.0 M HCl was added and thoroughly mixed. The solution was then filtered through 0.22 micron Millipore filter and 0.5 mL aliquots were dispensed into 10 mL autoclaved glass vials. The contents of the glass vials were frozen in a dry ice bath and subsequently lyophilized. Radiochemical purity (RCP) of the complex was determined by TLC in acetone and saline as well as by HPLC analyses (C18 reversed phase column, solvent A = water with 0.1% trifluroacetic acid; solvent B = acetonitrile with 0.1% TFA; Gradient - 0 min - 10% B, 5 min - ,10% B, 15 min - 25% B, 25 min - 25% B). Results: Conventional method of 188 Re(V)-DMSA preparation involves heating in boiling water bath for 30 min to obtain acceptable RCP. However, presence of oxalate in the reaction mixture could significantly enhance the complexation kinetics and acceptable level of RCP could be achieved by incubating at room temperature for 15 min. Under optimized conditions, 2 mg of DMSA, 5 mg of ascorbic acid, 5 mg sodium oxalate and 0.4 mg SnCl 2 .2H 2 O at pH 2, when incubated at room temperature for 15 min resulted in 188 Re(V)-DMSA complex with >95% RCP. Same formulation was subsequently transformed into a lyophilized kit. To prepare 188 Re(V)-DMSA using lyophilized kit, 1 mL of freshly eluted Na 188 ReO 4 was added to the vial and incubated at room temperature for 15 minutes. RCP of 188 Re(V)-DMSA was determined by TLC in acetone [R f ( 188 ReO 2 + 188 Re(V)DMSA) - 0; R f (Na 188 ReO 4 ) - 0.9] and saline [R f ( 188 ReO 2 ) - 0; R f ( 188 Re(V)DMSA + Na 188 ReO 4 ) - 0.9]. HPLC analysis of 188 Re(V)-DMSA complex prepared using the kit showed a mixture of four isomers which is as expected and also consistent with earlier reports. However, we observed that the ratio of the isomeric species formed are not the same as in the case of 188 Re(V)-DMSA prepared by conventional method and using the oxalate method. Conclusion: A single vial lyophilized kit for preparation of 188 Re(V)-DMSA at room temperature was developed. Using these kits, 188 Re(V)-DMSA could be prepared consistently in RCP >95%. Impact of difference in the isomeric ratio in 188 Re(V)-DMSA prepared by conventional method, without oxalate, and kit method can be ascertained only after comparing their in vivo distribution.
Elution profile of 188 Rhenium Generator
Priyanka K, Ajit Shinto, Kamaleshwaran,
Radha Krishnan, Indira V. Upadhya, Aswathi, Vyshak
Department of Nuclear Medicine, KMCH, Avinashi Road, Coimbatore - 641 014, Tamil Nadu, India
Background :Rhenium-188 (Re-188) is a high energy ß-emitting radioisotope obtained from the tungsten-188/rhenium-188 (W-188/Re-188) generator, which has shown utility for a variety of therapeutic applications in nuclear medicine, oncology, and interventional radiology/cardiology. Re-188 decay is accompanied by a 155keV predominant energy γ-emission, which could be detected by γ-cameras, for imaging, biodistribution, or absorbed radiation dose studies. Aim: A graph made to show how much material is carried out of the column by the eluent in column over time. The graph will show a number of different peaks; each peak represents a different separated material from the original mixed substance. Materials and Methods: Rhenium -188 generator GREN-1 is intended for multiple production of sterile pyrogen -free solution of sodium perrhenate with eluate. ITG W-188/Re -188 generator based on alumina column.Radionuclide is eluted from the generator with sterile isotonic solution as sodium perrhenate in volumes indicated. Result: Yields were determined by measurement of the total activity extracted in a given elution time and calculation of the ratio between this value and the activity calculated from parent activity in the same units and same time elapsed since previous elution.Elute values are noted and elution profile is done. Conclusion: A major challenge in the successful development of 188W/188Re generators for clinical application is the low radioactive concentration of the eluted 188ReO4 - solution which is often encountered for the commonly used adsorptive type column generator, this results from the large alumina columns needed for adsorbing sufficient quantity of the invariably low specific activity 188W.
Nivya Thomas, Radhakrishnan ER, Indira V Upadya, Aswathy KK, Vyshak Mohan, Kamaleshwaran, Ajith Shinto
Department of Nuclear Medicine, KMCH, Avinashi Road, Coimbatore - 641 014, Tamil Nadu, India
Background and Aim : Rhenium-188 hydroxyethylidine diphosphonate (HEDP) is a new and attractive radiopharmaceutical that localizes in skeletal metastases and emits beta particles that may be therapeutically beneficial. In this study, the therapeutic efficacy of Re-188 HEDP was investigated in an uncontrolled initial trial of 61 patients with different types of advanced cancer for the palliation of painful bone metastases. Materials and Methods: Sixty-one patients with painful bone metastases of lung, prostate, breast, renal, rhinopharyngeal, and bladder cancers were treated with 1.1 GBq (31 mCi) to 6.9 GBq (188 mCi) Re-188 HEDP. After treatment, the patients were followed at weekly intervals for the first 2 months and monthly thereafter for as long as 1 year. Hematologic function tests were also performed before and after treatment for 6 weeks. Pain responses were scored according to a three-point pain-rating scale as complete, significant, and minimal. Results: Prompt and significant relief of bone pain occurred in 80% of patients overall. Of the specific tumor types, pain relief was achieved in 77% of patients with lung cancer, in 80% with prostate cancer, in 83% with breast cancer, in 100% with bladder cancer, in 50% with renal cancer, in 50% with rhinopharyngeal cancer, and in 87% of patients with other tumor types, with no severe side effects or hematopoietic toxicity. Conclusion: This large clinical trial verified that Re-188 HEDP is a useful radiopharmaceutical agent to treat painful bone metastases from various tumor types.
117 Lu Labeled Hydroxyapetatite (117 Lu Ha) In Radiosynovectomy
Beven George, E.K.Radhakrishnan, Indira V Upadhya, Aswathy K.K, Mr.Vyshak, K.K. Kamaleshwaran, Ajit Shinto.
Department of Nuclear Medicine,KMCH, Avinashi Road,Coimbatore - 641 014, Tamil Nadu, India
Background and Aim: To evaluate the use of radiosynovectomy using Lu-177 labeled hydroxyapatite(Lu-177 HA)in the treatment of knee joints in rheumatoid arthritis(RA). Materials and Methods: 22 patients,diagnosed with RA and suffering from synovitis of the knee joints where reffered for RS and where followed up for period of one year.The duration of the disease was 11.2+/-10 months.15\22 kness had pain during the night and 10\22 had abnormal flexibility.Three phase bone scintigraphy(BS3)of knee joint was performed to confirm active synovitis and RS was performed according to the EANM guidelines.All were treated with 333+/-46 MBq of Lu-177 HA administered intra articularly.Monitoring of activity distrubution was performed by static imaging of knee joint.They were evaluated clinically at one year after the treatment by considering the pain improvement from baseline values in terms of 100 point visual analog scale(VAS),the improvement of knee flexibility and the pain remission during the night.RS response was classified as poor(VAS <25),fair(>/=25-50),good (>/=50-75) and excellent(>/=),with excellent and good results considered as success,while fair and poor as failure.BS3 was repeated after one year and changes in the second phase of BS3 were asessed visually,using a 4-degree scale and third phase,semiquantitatively with J/B ratio to see the response. Results: One year after treatment,the VAS% improvement from baseline was 90%+/-5.2 % and found to be significantly related to patients age(P=0.01),during of the disease(P=0.03).The overall sucess rate(VAS>/=50)was 90%.Remision of pain during the night acheived in 100% and knee flexibility improved in 80%.The changes in the blodd poll phase before RSV were 3.8+/-0.5 andafter 0.8+/-0.4(p<0.001).The J/B ratio was before RSV 2.8+/-0.5;after treatment 1.0+/-0.3(P<0.001.The J/B ratio was before RSV 2.8+/-0.5;after treatment 1.0+/-0.3(p<0.05).RS sideeffects were minor and not significant. Conclusion: RSV with Lu-177 HA was safe and effective in patients with knee joint synovitis of rhematoid origin.They show significant therapuetic effect after one year follow-up peroid with no significant side effects.Controlled clinical trails are necessary to evaluate therapeutic efficacy and safety compared to teatment with other radionuclides and steroids.
Bone pain palliation using 177 Lu EDTMP
Albin K J, E K Radhakrishnan, Indira V Upadya, Aswathy K K, Vysakh, Ajit Shinto, K K Kamaleswaran
Department of Nuclear Medicine, KMCH, Avinashi Road, Coimbatore - 641 014, Tamil Nadu, India
Background and Aim: Bone pain palliation using 177 Lu labeled EDTMP. Methods: 10 patients with disseminated skeletal metastases received a single bolus infusion of 177Lu EDTMP(3.7GBq).All patients had painful bon metastases in more than one anatomic region that were not relieved by narcotic analgesics. The efficacy of the agent was studied by following pain scores assessed at base line and at 4,8 and 12 week after therapy,by using Karnofsky indices and mobility scores,and by determining the requirement for analgesics at base line and 4 week after therapy. The toxicity of the agent was assessed by analyzing complete blood count. Results: A significant reduction in the mean case score of 8.44 dropped to 5.73 within 1 month of treatment. Six patients who required analgesics for pain management had either reduced or completely withdrawn from their use by 4 week. Compared with initial scans, scans obtained 1month after therapy also showed a decrease uptake of the radiotracer. The mobility scores of all patients were higher at 4week the mean Karnofsky performance score of all patients was initially 45 and increased markedly to 69 al 4 week none of the patients experienced blood related toxicity. Conclusion: 177 Lu EDTMP with only low bone marrow toxicity provided significant pain relief to patients and considerably increased their mobility, resulting in an overall improvement in the quality of life the results of the preliminary clinical study indicate that 177Lu EDTMP can be considered an effective and safe therapeutic radiopharmaceutical or pain palliation with disseminated skeletal disease.
Quality control of Re-188 HEDP AND Re188 tin colloid
Sona ShajiI, Radhakrishnan ER, Indira V upadya, Ashwathi KK, VysakMohan, Kamaleshwaran, AJit Shinto
Department of Nuclear Medicine, KMCH, Avinashi Road, Coimbatore - 641 014, Tamil Nadu, India
Background and Aim: The purpose of this study was to perform the qualiy control of Re188HEDP and Re188tin Colloid. Materials and methods: QC of 10 preparations of Re188 HEDP and tin Colloid were performed over a period of 2 months.For the preparation of HEDP kit:add required activity (Re188) in to the HEDP kit.Then add perrhenic acid to it.shake well and heat for 35-45min.Then add buffer.For the QC of Re188 HEDP:useITLC SG strip and the solvent is acetone and saline.% of RHR R f =0(saline strip) % of perrhenate R f =1.0(acetone strip).For the preparation of Re188tin Colloid:add required activity(Re188)in to the stannous solution.mix well,cap the vial and heat for 2hr.Then add phosphate buffer.For the QC of tin Colloid:use ITLC SG strip and solvent is saline.% of purity R f =1.0 and % of impurity R f =0. Results: For all the 10 preparation,radiochemical purity was found to be abpve 95%. Conclusion: From the above result,Re188 HEDP and tin Colloid can be used for human administration.
Quality Control of 188 Re Lipiodol
Riya George, Radhakrishnan ER, Indira V Upadya, Aswathy KK, Vysak Mohan, KK Kamaleswaran, Ajit Shinto
Department of Nuclear Medicine, KMCH, Avinashi Road, Coimbatore - 641 014, Tamil Nadu, India
Background and Aim : The objective of this study was to perform the quality control of 188 Re Lipiodol. Materials and Methods: QC of 10 preparations of 188 Re Lipiodol(5 SSS and 5 HDD) were performed over a period of 2 months. For the preparation of HDD kit;add required activity ( 188 Re) into the HDD kit and heat for 1 hr. Add lipiodol ,centrifuge,and separate the lipiodol phase for use. For the QC of HDD lipiodol;Use ITLC SG strip and the solvent is acetone and saline. %colloid R f- 0.0(Acetone) and %perrhenate R f- 1.0(saline).For the preparation of SSS kit;It has two kit vial, vial A and vial B. Add activity to vial A and shake the vial for 15 min and transfer content in vial B to vial A. Heat for 15 min, add lipiodol ,centrifuge, separate the lipiodol for use. For QC of SSS lipiodol; Use the TLC strip , the solvent is a mixture of hexane and dichloro methane (6:4). 188 Re SSS R f -0.7, 188 ReO 4 Na R f -0. Results: For all the 10 preparation, Radio chemical purity was found to be above 95%. Conclusion: From the above result 188 Re Lipiodol can be used for the administration.
99mTc TRODAT in the evaluation of Parkinson's disease
Gayathri A, Radhakrishnan Er, Indira V. Upadya, Aswathi KK, Vysakh Mohan K
Department of Nuclear Medicine, KMCH, Coimbatore - 641 014, Tamil Nadu, India
Background and Aim: Tthe purpose of this study was to investigated the potential use fullness of 99m Tc-TRODAT-1 magingin the evaluation of patients withPD disease. Materials and Methods: Sixteen patients with PD were enrolled in this study (9 men, 7 women; Mean (SD) age - 64 (10.4) years). PD was diagnosed according to generally accepted criteria.A dose of 740-814 MBq (20-22 mCi) 99mTc-TRODAT-1 in normal saline solution was injected intravenously into each patient soon after 3hrs ,the images were obtained. Specific uptake in the striatum and its sub-regions, including the putamen and caudate nucleus was calculated and tha ratios of specific striatal bindig to nonspecific occipital binding were calculated.Patients were examined in the supine position with a head holder to avoid motion. SPECT/computer tomography (CT) images were acquired 3 h later by using a Siemens dual-head-camera, with low energy high-resolution collimators and 64 equally spaced projections over 360°, 30 s/step and using a 128 × 128 matrix size. Results: The formulated kit was found to be pharmaceutically pure when tested for sterility and endotoxin. The radio-chemical purity of prepared 99mTc-TRODAT-1 were >90% and remained stable up to 2 hr. The images were interpreted both visually and by semiquantitative analysis. In the dynamic studies, we found that radioactivity accumulated in the basal ganglia area of each subject. On SPECT images, a better contrast of radioactivity between the striatum and adjacent brain tissue was observed in healthy volunteers than in patients. Conclusion: This study showed that 99m Tc-TRODAT-1 SPECT is a safe, convenient and reliable tool for measuring DATs and for evaluating and monitoring nigrostriatal degeneration. Although the clinical rating scales and DAT SPECT imaging have some limitations, the complementary measurements of mean ratio of specific striatal-to-nonspecific uptake of 99m Tc-TRODAT-1 by SPECT should provide adequate monitoring of disease progression and evaluation of potential neuroprotective effects. Our results confirm the potential of using 99m Tc-TRODAT-1 for DAT measurement, and staging the patients, which is clinically important for the early diagnosis of PD.
131 I Capsule Counting On Planner Gamma Camera System- An Alternative Approach
Biju K, Awasare SU, Baghel NS, Rajan MGR
Radiation Medicine Centre, BARC, TMC Annexe, Parel, Mumbai - 400 012, India
Background: Thyroid gland uptake of radioactive 131 I is a well-established nuclear medicine procedure to assess thyroid function. Low-dose 131 I (25 - 100µCi) is orally administered to the patient for 131 I-uptake in thyroid gland its scan. In order to obtain the uptake percent in the thyroid, the 131 I capsule counts are taken before oral administration. Low dose diagnostic dose like 25uCi and 100uCi are supplied as capsules and it is essential to count each capsule individually to confirm that the quantity of 131 I in it is within acceptable limits for patient use. Aims: To use the planar gamma camera to scan all the 131 I capsules received and assess them for uniformity and compare with the thyroid uptake probe, where the capsules are counted individually. Materials and Methods: 25uCi (15 No.) are received from BRIT weekly for patients' use. We have carried out this as preliminary study with 25 uCi capsules only. Thyroid uptake probe (Nuclear Chicago Company) was calibrated for 131 I and the capsules were counted individually for 10 sec each (after numbering each capsule). The capsule was kept at 30 cm from probe as per SOP. The 15 capsules were then arranged on thermocol sheet with cavities cut in it with minimum 8cm distance between them. One capsule was placed in each cavity. The distance between them was required to minmize scatter counts due to collimator's septal penetration. The capsules were scanned using planner gamma camera attached with high energy collimator (Siemens 5/8" crystal Symbia Dual Head Gamma Camera System) for 100 sec. This study, with both the probe and the camera was carried out with another two batches of 131 I-capsules received in the subsequent two weeks. Results: Camera based capsule counts obtained by drawing Region of Interest (ROI) around each capsule and counts observed using thyroid uptake probe of 15 capsules were tabulated. Mean and standard deviation (SD) of all counts from camera based method were compared with that of probe based method. Correlation was found to be significant between capsule counts taken by these two different methods for all 3 sets of capsules. Conclusions: Camera based 131 I-capsule counting method is an easy and time saving method compared to probe based capsule counting. It can provide uniformity information for a batch of 131 I-capsules and avoid the time consuming method of individual capsule with the thyroid uptake probe.
| Thyroid and Endocrine Imaging|| |
Utility of 99m Tc HYNIC-TOC SPECT/CT in neuroendocrine tumors
Abinaya S, Ajit Shinto, Kamaleshwaran, Radha Krishnan, Indira V. Upadhya, Aswathi, Vyshak
Department of Nuclear Medicine, KMCH, Coimbatore - 641 014, Tamil Nadu, India
Background and Aim: The objective of this study was to evaluate the use of 99m Tc HYNIC-TOC SPECT/CT in the diagnosis staging and management of gastroenteropancreatic neuroendocrine tumors (GPNETs). Materials and Methods: 40 patients (median age, 55 years)with histologically proven GPNETs underwent 99m Tc HYNIC_ TOC whole body scintigraphy and regional SPECT/CT as indicated. Images were evaluated by two experienced nuclear medicine physicians both qualitatively as well as semi quantitatively (tumor to background and tumor to normal liver ratios on SPECT/CT images).Results of SPECT/CT were compared with the results of conventional imaging. Histopathology results and follow up somatostatin receptor scintigraphy with 99m Tc HYNIC-TOC or conventional imaging with biochemical markers were considered to be the reference standards. Results: 10 patients had pancreatic tumor with liver metastasis,15 patients with liver and bone metastasis, 8 patients had lung metastasis and other 7 patients with nodal metastasis.99m Tc HYNIC-TPC showed sensitivity and specificity of 92.5% and 90.7% , respectively, for primary tumor and 98% and 89% for metastasis.It showed better results than conventional imaging modalities for the detection of both primary tumor (P<0.001) and supported management decisions in 10 patients (25%) Conclusion : 99m Tc HYNIC TOC SPECT/CT appears to be a highly sensitive and specific modality for the detection of GPNETs.It is better than conventional imaging for the evaluation of GPNETs and can have a significant impact on patient management and planning further therapeutic options.
Tc99m Pertechnetate Scan and Ultrasonography Correlation In Congenital Hypothyroidism
Harshul Sharma, Nikhil Seniaray, Arpana Arbind, Sulumo Ejanbemo Ezung, Abhinav Jaimini, Maria M D D'souza, Sanjeev Saw, Santosh Pandey, Dinesh Kumar, Rajnish Sharma, Anupam Mondal
Institute of Nuclear Medicine and Allied Sciences, Defence Research and Development Organisation, Delhi, India
Background: Congenital hypothyroidism (CH) or cretinism is a condition of thyroid hormone deficiency present at birth. Approximately 1 in 4000 newborn infants has a severe deficiency of thyroid function, while even more have mild or partial degrees. Congenital hypothyroidism is the most common cause of acquired mental retardation. Tc 99 static scan is good investigation which can complement USG and thyroid blood profile in determining etiology and prognosis of patient. Material and Methods : 20 patients were selected with raised TSH level done within 3 to 7 days of birth. Patients were then subjected to ultrasonography (USG) neck and 99m-Technitium static scan with 1 millicurie of radioactivity which was done on Symbia T2 true point Gamma camera. All the patients were started medication within first 20 days of birth. Results : In accordance to the findings of USG neck, Thyroid profile and USG neck patients were divided in following groups
1: Ectopic thyroid gland: Ectopic gland seen on both ultrasonography and Tc99 scan.
2: Thyroid agenesis: Patients were negative on both ultrasonography and Tc99 scan
3: Dysharmonogenesis: Patients which were positive on ultrasonography and Tc99 scan
4: Interference due to maternal antibodies, Na symporter defects or any other genetic defect: Patients which were positive on ultrasonography and negative on Tc99 scan.
Group I: 3 Patients
Group II: 5 Patients
Group III: 5 Patients
Group IV: 7 Patients.
Conclusions : Correlation of thyroid scintigraphy and USG neck with blood T4 and TSH levels allows specific etiological diagnosis in the majority of cases of congenital hypothyroidism.
Atypical Parathyroid Adenoma With Brown Tumors As Initial Presentation - A Rare Entity
Krishna Mohan V S*, Ramya Priya R*, Ranadheer Mantri*, Manishi L Narayan*, Alok Sachan**, Tekchand Kalawat*
*Department of Nuclear Medicine and PET CT, **Department of Endocrinology, Sri Venkateswara Institute of Medical Sciences, Tirupati - 517 507, Andhra Pradesh, India
Background: Primary hyperparathyroidism is a disorder caused by over production of parathormone (PTH). The clinical signs and symptoms are mainly due to abnormality in calcium, phosphate, and bone metabolism. Increased levels of PTH results in hypercalcemia and hypo phosphatemia. Initial presentation in many cases includes recurrent nephrolithiasis (10-25%), neuropsychiatric disturbances, peptic ulcers and less frequently, extensive bone resorption resulting in multiple fibrotic cystic lesions (brown tumors). Here, we report a case of multiple brown tumors in a primary hyperparathyroidism patient. Case History: A 21 year female, presented with generalized bone and body pains with history of medical treatment eight months ago for a hard bony lesion, developed in left side clavicle region. She was diagnosed as Fibrous dysplasia and received single dose of Zoledronic acid in January 2015. During follow up, she had no relief in pain symptoms and referred for our institute, to Department of Endocrinology and bone metabolism. After clinical examination and other routine blood tests, she was diagnosed to have pathological fractures and was referred for radionuclide whole body bone scintigraphy. Bone scintigraphy findings show, diffuse increased radiotracer uptake in bone with multiple moderate intensity osteoblastic bone lesions, involving left clavicle, left humerus, right humeral mid shaft and bilateral tibia and raised strong suspicion of hyperparathyroidism with possibility of multiple brown tumors. Following this, patient was examined with dual phase, Tc99m methoxy isobutyl isonitrile (MIBI) parathyroid scintigraphy, which show focal lesion with increase MIBI concentration just below the left lobe of thyroid, suggestive of left inferior parathyroid adenoma, which was excised and histo-pathologically examined and reported as atypical parathyroid adenoma. Conclusion: Functional parathyroid adenoma causes diffuse bone mineral changes in most of the patients. Focal bone lesions (brown tumors) are rare and often produce a diagnostic dilemma. Early and proper diagnosis of brown tumors will significantly reduce risk of fracture and related morbidity.
Occurrence of second primary neoplasms in patients with differentiated thyroid cancer treated with radioiodine
Nishikant Avinash Damle, Chandrasekhar Bal,
Ravikant Gupta, Praveen Kumar, Madhav Yadav,
Sameer Taywade, Geetanjali Arora
Department of Nuclear Medicine, All India Institute of Medical Sciences, New Delhi, India
Background: Differentiated thyroid cancer (DTC) is a relatively indolent malignancy and with the current therapeutic strategy of surgery, followed by I-131 ablation and suppressive thyroxine therapy, the 5yr survival exceeds 90%. However, second primary neoplasms (SPN) have been seen to occur in some of these patients during follow up. In the previous decade, few studies proposed an association between 131-I therapy and occurrence of SPNs while many others refuted this. Aim: We aimed to assess the prevalence of second primary neoplasms in patients treated for DTC with radioiodine and their site of occurrence. Materials and Methods: 4712 patients, who received radioiodine therapy at the All India Institute of Medical Sciences between 1985 and 2012 for DTC, were included in the study. The data was analyzed retrospectively for occurrence of SPNs in these patients. All patients underwent thyroidectomy prior to radioiodine therapy. Low dose I-131 whole body scan was performed to determine site of disease. At our center, we follow a policy of empiric dosing following thyroid hormone withdrawal. Age, gender, histopathology, ablation dose, and subsequent I-131 treatments were recorded. Details of occurrence of the SPN including type, site, date of occurrence, treatment and time interval between the two neoplasms were reviewed. Results: A total of 44 cases [22 male, 22 female] of DTC with SPN were observed in our study. Mean age of these patients was 44.5 years (10-78 years). The most common site of SPN in these 40 patients was breast [10/40; 22.7%], followed by brain (including meningiomas) [8/44; 18.2%], nerve sheath tumor [3/40; 6.8%], ovary [3/40; 6.8%], Head and neck squamous cell [3/40; 6.8%] and Leukemia [3/40; 6.8%]. Lymphoma, adenocarcinoma prostate and renal cell carcinoma were found in 2 patients each [4.5%] while hepatocellular carcinoma; chondrosarcoma, rectal cancer, cervical cancer, angiomyolipoma, giant cell tumor, eosinophilic granuloma, Wilm's tumor were present in one patient each [2.5%]. Mean interval between diagnosis of the two malignancies was 62.9 months (1-360 months). Mean I-131 dose given to these patients was 132.93mCi. Of these 44 patients, 22 patients (50%) had SPNs after thyroid cancer while 22 (50%) had SPNs prior to the detection of thyroid cancer. Conclusion: Occurrence of second primary neoplasms is a well known occurrence in patients with differentiated thyroid cancer. Breast cancer was the most frequently associated malignancy followed by CNS tumors in our data. There appears to be no causal relationship between radioiodine therapy and the occurrence of these SPNs, however a meticulous follow up for a longer period may yield newer observations.
Retrospective Analysis of Thyroid Scintigraphy In Patients Presenting With Thyrotoxicosis In Tertiary Institute, Tirupati, In The Past 5 Years
Amrutha Lakshmi R*, Mehabunnisa Sk*, Ramya Priya R*, Krishna mohan VS*, Ranadheer Manthri*,
Manishi L Narayan*, Kalawat TC*, Alok Sachan**
*Department of Nuclear Medicine and PET-CT, **Department of Endocrinology, Sri Venkateswara Institute of Medical Sciences, Tirupati - 517501, Andhra Pradesh, India
Background: Thyrotoxicosis is the clinical syndrome of excess circulating thyroid hormones. To differentiate between various etiologies in patients presented with thyrotoxicosis, we propose 99m-Tc thyroid scintigraphy image guided work up for the purpose of diagnosis and treatment. Aim: To study the thyroid scintigraphic patterns in patients referred for detecting etiology of thyrotoxicosis to department of nuclear medicine SVIMS Tirupati. Materials and Methods: Retrospective analysis of thyroid scintigraphy done for de novo detected thyrotoxic patients in department of nuclear Medicine, SVIMS from 1 st November 2010 to 31 st August 2015. All patients who presented with thyrotoxicosis features and biochemically decreased serum TSH levels, increased or normal serum T3, T4 levels were included in the study. 99m-Tc thyroid scintigraphy was done following standard patient preparation and data acquisition guidelines. Scintigraphy images of all patients were interpreted by Nuclear Medicine physicians based on thyroid uptake, thyroid to parotid ratio, any increased or decreased focal areas of uptake. Results: Total number of patients available for analysis were 1230. Of which, 791/1230 (64.3%) were Grave's disease, 200/1230 (16.2%) were Sub acute thyroiditis, 45/1230 (3.6%) were Autonomously functioning thyroid nodule, 88/1230 (8%) were Toxic multi nodular goitre, 86/1230 (4.5%) were Graves with solitary cold nodule, 20/1230 (1.6%) were unilobar hyperfunction. Conclusion: 99m Tc Thyroid scintigraphy is a useful investigation in diagnosing etiology of thyrotoxicosis and help in management and choosing management options. Incidence of sub-acute thyroiditis is high in this region.
Management of Papillary carcinoma of thyroid with pulmonary metastases in Institute of Nuclear Medicine and Allied Sciences Rajshahi - Two Case Reports.
K Z. Shah 1 , N. Begum 2 , M. Hossain 2 , P. Ahmed, S. I. Chaudhuary 2
Institute of Nuclear Medicine and Allied Sciences, Rajshahi, Bangladesh
Background : Thyroid cancers are the most common endocrine malignant tumors. Papillary thyroid carcinoma (PTC) is the most frequent type with a ratio of 80%. PTC commonly metastasizes to regional lymph nodes. However, distant metastasis may rarely occur and account for 5% of the patients. The lung and the bones are the most common sites for distant metastases. In case of distant metastasis is approximately 25-40 yrs survival rate %. Lifelong follow up is needed in all DTC as because life time recurrence rate is relatively high, reaching 10-30% in some series. . Case Report -I: A 23 Yrs old unmarried female patient referred to our institute for radio-iodine ablation. She was a diagnosed case of papillary carcinoma of thyroid. All investigations were done; necessary before radio-iodine therapy. She treated with 138 mci of I 131. . During follow up all investigations were done according to Ca -thyroid management protocol. Results were very good. She discontinued follow-up. Consequently she developed respiratory problem respiratory since 2014. All investigations were done including chest X Ray. X Ray showed multiple patchy opacity in both lung fields. LDS (RxWBS) showed pulmonary metastases. Again she underwent radioiodine ablation and followed by LT4 therapy. We advised her for lifelong follow up. Follow-up result was excellent. In June 2015 - LDS was done (result was negative). Case Report -2: A 20 years man, known case of papillary carcinoma of thyroid with local nodal metastases was send us for treatment of Ca-thyroid followed by radical neck dissection. His LDS showed residual functioning thyroid tissue in thyroid bed and radio iodine uptake in upper part of right lung parenchyma (Pulmonary Metastasis). He had some respiratory symptoms. X-Ray chest revealed patchy opacity in upper zone of right lung. He was radio ablated with LT4 therapy. Regular follow-up was done. No patchy opacity detected in chest X-Ray. LDS was performed after 12 months -Negative Scan. Conclusion: Metastatic PTC is an uncommon condition that generally has a relatively good prognosis. However in case of severe tumor burden and widespread metastases.The prognosis may be poor. We highlight proper treatment and management of the patient with pulmonary metastases.
Imaging and Followup of 188Re Lipiodol Intra Arterial Therapy for Inoperable Hepatocellular Carcinoma
Neenu T. paul, Ajith Shinto, K. K. Kamaleswaran, E. K. Radhakrishnan, Indira V. Upadya, Aswathy KK, Vyshakh
Department of Nuclear Medicine, Kovai Medical Centre Hospital, Coimbatore, India
Background and Aim: Studies have proven the safety and efficacy of trans-arterial rhenium-188 HDD conjugated lipiodol (radioconjugate) in the treatment of patients with inoperable hepatocellular carcinoma (HCC). Materials and Methods : The radioconjugate was prepared by using an HDD (4-hexadecyl 1.2, 9, 9-tetramethyl-4,7-diaza-1,10-decanethiol) kit developed in Seoul National University Korea, and lipiodol. A WARMTH team headed by Dr. Ajit Padhy were in Coimbatore, India to help us set up the protocol and radiochemistry in the month of August 2013. Over a period of 18 months, 30 patients with inoperable HCC or metastatic liver lesions received at least one treatment of radioconjugate. Only 4 patients were re-treated for residual active lesion or new lesions. The level of radioconjugate administered was empiric with a range of doses between 60 to 200 mCi. Patients were followed for at least 12 weeks after therapy, until recovery from all toxicity. The clinical parameters evaluated included toxicity, response as determined by contrast-enhanced computed tomography, palliation of symptoms, overall survival, performance status (Karnofsky) and hepatic function (Child's classification). Liver function tests, serum alfa-fetoprotein (AFP) levels and complete blood counts were done at each follow-up visit. Results: Of the 30 patients treated so far, 28 are still alive and do come for regular follow up. All of them report good quality of life. Median survival has not been reached. Side-effects were minimal and usually presented as loss of appetite, right hypochondrial discomfort and low-grade fever, even at high levels of administered radioactivity. The symptoms resolved with simple supportive therapy within 3 days of onset. Liver function tests at 24 and 72 h showed no significant changes and complete blood counts at 1 week, 4 weeks and 12 weeks showed no changes (no bone marrow suppression). Survival at 6 months was 100%. We could achieve biochemical or imaging stability of disease in almost 50% and partial or complete regression in another 35% patients approximately. Conclusion: The results of this study show that 188 Re-lipiodol is a safe and cost-effective method to treat primary HCC or metastatic liver lesions via the transarterial route. In terms of efficacy, it is potentially a new therapeutic approach for further evaluation by treatment of larger numbers of patients. In addition we have developed in house labelling procedures for Re 188 HEDP/V DMSA and SN colloid for radiosynovectomy to make the Re generator more commercially viable. We have also implemented endovascular brachytherapy with Re 188 filled balloons to prevent in-stent restenosis in patients undergoing femoral/iliac artery stenting. There are multiple centres in the country and in the developing countries who have requested us to impart knowledge as well as training to set up a similar facility and we are enthusiastic in serving as the nodal training centre in taking this modality forward. The 1st world Rhenium congress to be held in Coimbatore, India in conjunction with WARMTH has been envisaged with a similar purpose in mind, i.e., to give a hands on experience to the delegates and engender confidence to explore the potential utility of Re 188.
| Central Nervous System|| |
Limbic Encephalitis Detected on 18 FDG - PET/CT scan while suspected for conversion disorder
Manishi L. Narayan, Thota Naveen 1 , B.Shivanand 2 , Krishna Mohan VS, A. Y. Lakshmi 3 , B. Vengamma 1
Departments of Nuclear Medicine, 1 Neurology, 2 Psychiatry, 3 Radiology, Sri Venkateswara Institute of Medical Sciences, Tirupati, Andhra Pradesh
Background and Aim: Diagnosis of dementia syndromes and neurodegenerative disorders can be challenging for clinicians, especially in the early stages of disease, if associated with other comorbid neuropsychiatric conditions and also with use of certain medications. Positron emission tomography (PET-CT) with 18 F-Fluorodeoxyglucose (FDG) allows detection of neurodegenerative disorders earlier than is otherwise possible. Awareness of other conditions that can cause cognitive impairment and altered metabolism, such as autoimmune paraneoplastic and encephalitic syndromes, is vital when interpreting brain FDG - PET/CT scan. Clinical signs and symptoms of LE are non specific. An early and precise diagnosis of Limbic Encephalitis (LE) is very important, as delay can have significant impact on clinical management because the illness can be fatal if left untreated with immunosuppression. Materials and Methods: We are presenting a 63 Yrs. male, known diabetic, hypertensive, Ex smoker and Ex Alcoholic. Presented to Hospital with history of irritability, irrelevant talk and respond to command, associated with aggressive behaviour for 5 months duration. For which first he was evaluated by psychiatrist and subsequently referred to Department of Neurology with progressive symptoms, multiple episodes of complex partial seizures and memory disturbances. His CSF analysis was inconclusive, resting awake EEG showed abnormal asymmetrical bilateral frontotemporal delta activity. MRI and CT imaging revealed age related cerebral atrophy with deep white matter ischemic changes. He was suspected for neuropsychiatric disorder, possibly conversion disorder. Therefore, patient was sent for 18 F-FDG PET/CT Brain scan. Results: Brain 18 FDG -PET/CT scan revealed intense hypermetabolism in Left mesial temporal cortex, involving left amygdala and entire length of left hippocampus with max.SUV 41. Mild focal hypermetabolism was also seen in left lateral temporal cortex. Additionally, there was generalized reduced FDG uptake in remaining cortex. On whole body 18 FDG -PET/CT imaging, there was no other significant lesion seen in the body. Subsequently paraneoplastic workup was also done and anti-Neuronal Antibody (Paraneoplastic, NMDA) profile, was negative. His CSF, HSV - PCR and Serum TPO antibodies were also negative. Based on scan and clinical findings diagnosis of 'Autoimmune Non Paraneoplastic Limbic Encephalitis' was considered. Patient was treated symptomatically with steroids and antiviral therapy (Methyl prednisolone, Acyclovir and Valproate). He showed improvement before discharge from hospital and on subsequent follow up. Conclusion: 18 FDG-PET/CT plays an important complementary role in diagnosis of LE. Limbic Encephalitis frequently manifest as FDG hypermetabolism, most frequently involving medial temporal lobe. Additional involvement of cortices and cerebellum can also be seen. Dedicated Brain and whole body FDG-PET/CT imaging is a non-invasive reliable tool that can provide unparalleled information for early, more accurate diagnosis of Limbic Encephalitis and can also be useful in detection of occult primary lesion. Hence, it ultimately helps in the patient management remarkably.
| Nuclear Medicine Physics|| |
Quantitative study on the effect of acquisition parameters on flood field uniformity of gamma camera
Sutapa Rakshit, Basant Malpani, S. K. Saxena # ,
Nawab Singh Baghel
Radiation Medicine Centre, BARC, TMH Annexe Building, Parel, # IP&AD, Bhabha Atomic Research Centre, Trombay, Mumbai, India
Background and Aim: It is essential to assess the performance of Gamma Camera for its optimum performance before patient use. Gamma Camera Uniformity is one of the most important performance parameter that expresses the overall system performance either qualitatively or quantitatively. Evaluation of system non-uniformity is an essential practice in daily quality control procedure as suggested by NEMA and IAEA. A visual inspection of images usually reveals only gross deviations in performances. To study the effect of acquisition parameters like (a) Total acquired counts, (b) Energy window and (c) Matrix size on integral flood field uniformity of Gamma Camera system. Materials and Methods: A flood phantom of dimension 74 cm × 54 cm × 4 cm made of perspex was filled with 30 mCi of 141Ce (γ = 145 KeV, 48%, t1/2 = 32.5 days) liquid source (supplied by BARC) in double distilled water and mixed thoroughly. Flood-phantom was placed facing the GE Infinia Gamma Camera fitted with LEHR collimator. Standard set of acquisition parameters used were matrix: 1024*1024, photo-peak: 140 KeV, energy window: 20%, total counts: 5M. Static images of the flood phantom were acquired by varying (a) acquisition times of 3, 4, 5, ….20 min corresponding total counts of 2.64M, 3.5M, 4.35M, 5.22M…. 17.52M, (b) window width 25%, 20%, 15%, 10% and (c) matrix size 1024*1024, 512*512, 256*256, 128*128, 64*64 while keeping other parameters constant. Integral uniformity was calculated for CFOV and UFOV using flood uniformity tool provided in Xeleris Software. The software obtained average maximum and minimum counts of 9 pixels for calculating integral uniformity. Results: (a) Integral uniformity (IU) values of CFOV corresponding to acquired counts of 2.64M, 3.5M, 4.35M, 5.22M, 6.07M, 6.94M, 7.81M, 8.68M, 10.44M, 13.08M, 17.52M were 5.17, 3.33, 3.65, 3.07, 2.81, 3.53, 2.37, 2.41, 3.14, 2.65 and 2.36% respectively. The results showed that uniformity improved with increasing total count as observed from a 3 point moving average of the uniformity values obtained as above. They were 4.05, 3.35, 3.18, 3.14, 2.77, 2.64, 2.73, and 2.72. (b) IU of CFOV for energy window 25%, 20%, 15%, 10% was 4.66, 2.84, 3.87 and 3.59. (c) IU of CFOV for matrix of 1024, 512, 256, 128, 64 was 2.84, 2.89, 3.04, 4.54, 2.73, respectively. Conclusion: Increasing total counts lead to improvement of IU values but not much gain is obtained beyond 7.8M in our study. Integral uniformity values were observed to be independent of energy window width and matrix size.
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