Year : 2015 | Volume
: 30 | Issue : 5 | Page : 10--28
|How to cite this article:|
. Oral Papers.Indian J Nucl Med 2015;30:10-28
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. Oral Papers. Indian J Nucl Med [serial online] 2015 [cited 2022 Jul 2 ];30:10-28
Available from: https://www.ijnm.in/text.asp?2015/30/5/10/170235
Role of cardiac fusion imaging (SPECT-CTCA) as a prognostic tool in cardiomyopathy patients
Gowri Sankar, Sanjay Gambhir, Prasanta K. Pradhan, Naveen Garg, Murthy Siddegowda, Arun Prasanth, Amit K. Singh
Department of Nuclear Medicine 1 and Department of Cardiology 2 , Sanjay Gandhi Post Graduate Institute of Medical Sciences, Lucknow, Uttar Pradesh, India
Background and Aim: Dilated cardiomyopathy (DCM) is a disorder characterised by enlargement of the left ventricular cavity along with systolic dysfunction. The most common cause is idiopathic followed by myocarditis and ischemic heart disease. Single photon emission computed tomographic myocardial perfusion imaging (SPECT-MPI) shows high sensitivity in diagnosing ischemic component in DCM patients but it has moderate specificity. Similarly computed tomographic coronary angiography (CTCA) has high negative predictive value in ruling out ischemic disease. To incorporate the duality of morphology and function and to overcome individual limitations fusion imaging was done. The aim of this study was to know the value of fusion imaging as a prognostic tool in cardiomyopathy patients. Materials and Methods: Thirty one patients clinically diagnosed by cardiologists to have DCM were included in this prospective study. They had no prior documented history of coronary artery disease (CAD). Initially they underwent stress-rest SPECT-MPI using Tc-99m labelled Sestamibi. Of this only 28 patients underwent CTCA subsequently. Fusion imaging was successfully done using CardIQ software (GE Healthcare). Only those patients who had matched perfusion defects to stenotic segments in fusion imaging were labelled as having CAD. All the patients were followed up prospectively post fusion imaging. Any cardiac events leading to hospital admission or cardiac death were considered as events. The effect of various parameters over event free survival was calculated using log rank test by Kaplan-Meier method. A p value of <0.05 was considered significant. Results: All the 31 patients who were initially included in the study were followed up for a median period of 6.5 months (range: 1 to 20 months; S.D: 6). Events occurred in five of the 31 patients (16%) the follow up period. Only three parameters, total calcium score (p=0.004), the nature of the perfusion defect (non viable, partially viable fixed defect, reversible ischemic and normal perfusion) noted in SPECT-MPI study (p=0.032) and the outcome of the fusion imaging (whether patient was labelled to have ischemic disease based on matched defects in fusion imaging or not) (p=0.038) were found to have a significant impact on event free survival in Kaplan-Meier survival analysis using log rank test. Conclusion: Fusion imaging may act as an independent prognostic marker in DCM patients, however longer median follow up period and larger multicentric prospective studies are required to validate these findings.
Role of Ictal and Inter-Ictal SPECT in Medically Refractory Epilepsy: Post-Surgical Correlation
Shwetal Uday Pawar, Ashmi Manglunia, Sangita Rawat, Gundu Hari Tilve
Department of Nuclear Medicine, Seth GS Medical College and KEM Hospital, Parel, Mumbai, India
Background and Aim : The non-invasive neuroimaging methods, such as single-photon emission computed tomography (SPECT), Video electroencephalogram (VEEG), and magnetic resonance imaging (MRI), has changed pre-surgical epilepsy evaluation. The purpose of this present study was to evaluate the role of ictal and interictal brain SPECT in pre-surgical localization of the epileptogenic focus and assess post-operative outcome. Methods and Materials : 740-1110 MBq (20-30 mCi) of Tc-99m ECD was injected during convulsion while being under VEEG monitoring for ictal brain SPECT study and the SPECT images were acquired after 30 minutes. The same procedure was repeated during interictal period. The reconstructed SPECT images were studied by the physician to look for the increased perfusion focus as epileptic focus and same area was studied in interictal SPECT study for normal or hypoperfusion. The correlation with MRI and VEEG was done. The ictal focus was concluded based on concordance of any two investigations out of the three. The post-surgical assessment was done by Engel's classification. Results : Using the Engel's outcome classification system as the standard of reference, MRI was correct in 46.6% (14/30) of patients. Inter-ictal EEG and Ictal-EEG were concordant with the surgical outcome in 36.66% (11/30) and 63.33% (19/30) of patients, respectively. SPECT shows the maximum concordance rate of 80% (24/30). The difference in the concordance rate of SPECT by Fisher's test when compared to both MRI and Inter-ictal EEG was statistically significant (P < 0.01). In patients with normal MRI findings, ictal SPECT showed accurate lateralization in 50% cases. However, ictal VEEG surpassed SPECT in patients with normal MRI and showed accurate localization in 2/2 cases (100%). Conclusions : In cases of epilepsy with bilateral MRI findings, perfusion SPECT is a useful modality for pre-surgical evaluation. Also, cases with discordant evaluation, SPECT can be employed as a supplementary tool for confirmation for seizure focus localization. SPECT also has a potential role in localizing the epileptogenic focus in patients with normal MRI.
Gastric Emptying Time Estimation in Normal Indian Infants (<1yr) and Its Correlation with Gastro Esophageal Reflux if any by Liquid Scintigraphic Method
Ashutosh Parashar, Shwetal U Pawar, Gundu Haridas Tilve
Department of Nuclear Medicine, Seth GS Medical College and KEM Hospital, Parel, Mumbai, India
Background and Aim : To estimate normal gastric emptying time (GET) in Indian infant (<1yr) population. To assess whether gastric emptying time is influenced by the presence of gastro-esophageal reflux (GER). Materials and Methods : Patients referred to our department for assessment of GER (n=149) underwent liquid scintigraphic GET estimation with age appropriate milk based formula feed. The infant feed [similac 1 for infants <6 months having protein: 14.5g, fat: 28.2g, carbohydrate: 49.4g providing 511kcal/100g and similac 2(for >6 months) having protein: 14.7g, carbohydrate: 56.8g, providing 466 kcal/100g]. Patients were given a dose of 1mCi/37mBq of 99mTc sulphur colloid via naso-gastric feeding tube followed by age appropriate volume of formula feed. Dynamic imaging was acquired for 1hr with static imaging at the end of 1hr and a delayed static image at the end of 2nd hr. Scans were done on gamma camera and interpreted by nuclear medicine physicians. Entire sample size was divided in four groups each of three months i.e 0-3mo., 3-6mo., 6-9m. & 9-12mo. All responses were tabulated and graphically represented wherever required. Statistical tools like mean, median, range, percentile, Chi-square were used. GET was calculated only from those studies which were negative for GER. Dynamic images were analyzed for the presence of reflux and whether it affects GET. Results : The mean GET in the age categories: 0-3mo, 3-6mo, 6-9mo and 9-12mo were 68.55min, 64.72mins, 66.62mins and 58.80mins respectively. No statistically significant relation was established between the presence of GER and liquid GET. GET for reflux positive patients was 66.26mins and GET in reflux negative patients was 62.41mins with standard error of mean 1.8 and 1.7 respectively. Conclusion : The mean liquid GET in Indian infant population is 62.41mins for GER negative individuals for the entire sample size. Individuals positive for reflux, have liquid GET of 66.26mins. In the present study no statistically significant relation was found between liquid GET and GER.
Evaluating varying patterns on cholescintigraphy indicative of chronic cholecystitis
Sudeshna Maitra , Natasha Singh , Madhuri Shimpi
Department of Nuclear Medicine, PD Hinduja National Hospital, Mumbai, India
Background and Aim: Liver and gall bladder (G.B.) diseases are two of the most common digestive system problems around the world. Chronic cholecystitis results from long standing inflammation resulting in loss of gall bladder function and can present as recurrent abdominal pain or dyspeptic symptoms requiring cholecystectomy. USG and HIDA imaging are often used in conjunction for establishing diagnosis of chronic cholecystitis. Our aim was to identify different patterns on cholescintigraphy favouring chronic cholecystitis. Materials and Methods: We evaluated HIDA scans performed for suspected biliary pain between the period July 2013 - July 2015. 100 patients were investigated. Of these, 65 had normal HIDA scan findings and 16 patients had absence of visualisation of gall bladder suggestive of cholecystitis and were treated accordingly. 19 patients (mean age 45 years), equal male : female ratio, had abnormal scan findings raising possibility of chronic cholecystitis. Of these, 15 patients had calculous disease. All patients were followed up by a review of electronic records and/or a telephone interview. The follow up period ranged between 2 months - 2 years. Result : Various scintigraphic patterns identified were delayed gall bladder visualisation with normal biliary to bowel transit , delayed biliary to bowel transit with normal gall bladder filling , faint or small sized gall bladder , poor contractile function of gall bladder with low ejection fraction ( <40 - 45 %) post fatty meal , normal gall bladder contractile function with small sized gall bladder and/or delayed gall bladder filling. 7 patients underwent laproscopic cholecystectomy with histopatholgy report conclusive of chronic cholecystitis, with resolution of symptoms post surgery. Amongst these 1 patient had demonstrated normal gall bladder contractile function, however size was small with delayed filling. Remaining 12 patients (of which 10 patients with calculous disease, and only 3 patients demonstrating adequate contractile function with small size and delayed filling of gall bladder) were on medical management for persistent intermittent episodes of mild symptoms with option of surgery reserved on recurrence of significant episode. Conclusion: Recognition of varying scinitigraphic patterns even in presence of normal contractile function of gall bladder with one or more of these patterns, rather than any solitary definitive finding, appears sensitive towards indicating possibility of chronic cholecystitis.
Role of Fatty Meal Augmented Hida Scan in Acalculous Biliary Symptoms
Unmesh Takalkar, Prafful Jatale, Ajay Rotte, Samir Joshi.
Department of Nuclear Medicine, United Ciigma Hospital, Aurangabad
Background: A hepatobiliary (HIDA) scan is an imaging procedure used to diagnose problems in the liver, gallbladder and bile ducts .Gallstones disease associated with biliary symptoms such as gallbladder dyspepsia (Episgastric discomfort, flatulence, intermittent nausea with fat intolerance), and biliary colic (abdominal pain Localized in the right upper quadrant) is commonly treated by cholecystectomy. In contrast, biliary symptoms in the absence of gallstones (acalculous biliary symptoms, ABS) often constitute a diagnostic and management challenge. Decision to recommend cholecystectomy to patients with ABS is sometimes based on abnormal cholescintigram, indicating biliary dyskinesia. Recently, the procedure has changed from intravenous intervention to fatty meal-augmented hepatic iminodiacetic acid (HIDA) scan to augment gallbladder contraction. Aim: To determine the long-term outcome of patients with ABS who underwent cholecystectomy based on abnormal cholescintigraphy using a new isotope study protocol of oral fatty meal augmentation of the gall bladder. Materials and Methods: A retrospective study of cholecystectomy was undertaken of all patients with ABS who were investigated with a fatty meal-augmented hepatic iminodiacetic acid (HIDA) scans between Jan.2014 till July 2015. Their case notes were reviewed. Pearson chi-squared test was used to analyse the relation between various parameters. Results: Overall, 22 patients had HIDA scans. About 19 out of 22 (86%) patients had abnormal cholescintigrams, but only 13 were recommended surgery. Two patients were excluded owing to cholelithiasis. Fourteen patients (64%) were considered cured 6 weeks later. However, seven (36%) patients failed to improve with surgery after an average follow up of 33 weeks. Out of the 6 patients with abnormal HIDA scans who were managed conservatively, 2 (41%) recovered spontaneously, and 4 (59%) remained unchanged. Conclusion: There is role of Oral fatty meal augmented HIDA scans in selecting patients with ABS for surgery. However, high false-positive rate should be kept in mind.
Clinical Production, Stability Studies and PET imaging with 16α-[ 18 F]Fluoroestradiol (16α- 18 F-FES): Current Status in India
Anupama Datta, Nitin Kumar, Ramgopal Meena, Swatantra, Lokendra Singh, Sachin Sony, Anil K Mishra
Institute of Nuclear Medicine and Allied Sciences, Defence Research and Development Organisation, Delhi, India
Background and Aim : Breast cancer remains the most common malignancy and a foremost cause of mortality in females worldwide. In India, breast cancer is now the most common cancer in most cities in India, and 2nd most common in the rural areas, one fourth (or even approaching one thirds) of all female cancer cases are breast cancers. The age shift (more young ladies affected),rising numbers of cases of breast cancer in India, late presentation (this directly decreases long term survival of the patients and lack of awareness and screening (screening is the single most important factor responsible for better survival of patients in the west) are some of areas which need urgent attention. In addition to early diagnosis, the understanding of oestrogen receptor (ER) levels in breast tumour is important for the prediction of disease prognosis and in deciding the appropriate treatment strategy. Oestrogens are the major role players in the initiation and progression of the breast cancer and approximately 75% of the tumours express the oestrogen receptor. Materials and Methods : Possibly for the first time in India, clinical production of 18F-FES has been carried out at Institute of Nuclear Medicine and Allied Sciences, Delhi. The synthesis of 16a- 18 F-fluoroestradiol was carried out using GE TRACERlab MX system with cyclic estradiol sulphate 3-O-methoxy -methyl-16b, 17b-epiestriol-O-cyclic sulfone (ABX) as precursor. Controlled synthesis of n.c.a. 16a- 18 F-FES was carried out by nucleophilic substitution in 72 minutes. Cartridge method was used for the purification of the tracer. 16a- 18 F-FES was produced in 17-25% radiochemical yield (decay corrected). Chemical and radiochemical purity is >95% and >99% respectively. Results : Studies suggests 16a- 18 F-FES is an oestrogen receptor (ER)-specific PET tracer with various applications. 16a- 18 F-FES PET is being routinely utilized for assessing the expression of oestrogen receptors in cancer patients. More than 50 patients have benefitted from it and it has proved to a dependable tracer for the evaluation and management of breast cancer patients. Conclusions : With high incidences of ER(+) breast cancer cases, PET imaging with 16a- 18 F-FES has proved to a useful tool not only in the diagnosis of primary cancer but a vital tool for catering the patients with history of ER-positive breast cancer in whom a clinical dilemma remained despite complete standard work-up (e.g., when imaging procedures were inconclusive and performing a biopsy was not feasible). This knowledge is not only helping in the design of therapeutic trials to improve treatment outcomes, but also has the long term potential to help clinicians plan, target, and evaluate therapies.
68 Ga radiopharmacy without expensive purification module: Preparation, evaluation and preliminary clinical utilization of 68 Ga-labeled NODAGA-RGD peptide derivative follwing 'mix and use' approach
Sudipta Chakraborty 1 , Rubel Chakravarty 1 , H. D. Sarma 2 ,
Rakhee Vatsa 3 , Priya Bhusari 3 , Jaya Shukla 3 , Bhagwant R. Mittal 3 , Ashutosh Dash 1
1 Isotope Production and Applications Division, 2 Radiation Biology and Health Sciences Division, Bhabha Atomic Research Centre, Trombay, Mumbai - 400085, 2 Department of Nuclear Medine, Post Graduate Institute of Medical Education and Research, Chandigarh - 160 012, India
Background and Aim: The present study is designed to demonstrate a 'mix-and-use' approach for radiolabelling RGD peptide derivative with 68 Ga without the utilization of expensive purification module offered by the commercial suppliers along with 68 Ge/ 68 Ga generators. As a proof of concept, 68 Ga-labeled NODAGA-coupled dimeric cyclic RGD peptide derivative [NODAGA-(RGD) 2 ] was formulated using 68 Ga eluted from 4 different 68 Ge/ 68 Ga generators without using any purification module. The radiotracer was successfully used for positron emission tomography (PET) imaging of breast cancer in human patients. Materials and Methods: The optimized conditions for radiolabelling NODAGA-coupled dimeric cyclic RGD peptide derivative NODAGA-(RGD) 2 with 68 Ga were ascertained using 68 Ga obtained from commercial 68 Ge/ 68 Ga generators from Eckert & Ziegler Isotope Products, Germany; iThemba, South Africa; ITG, Germany; and CeO 2 -PAN composite sorbent based generator developed in house. In all the cases, 68 Ga eluted from the generators was directly used for radiolabelling and no purification module was used. Preclinical studies were carried out in C57BL/6 mice bearing melanoma tumours. The radiotracer was prepared in a hospital radiopharmacy using 68 Ga obtained from ITG generator and used for monitoring breast cancer patients by PET imaging. Results: 68 Ga-NODAGA-(RGD) 2 could be prepared with high radiolabelling yield (>97%) and specific activity (~ 50 GBq/μmol) within 5 min at room temperature by mixing 68 Ga with the solution of the peptide conjugate, using 68 Ga eluted all four 68 Ge/ 68 Ga generators. In vivobio distribution studies showed significant uptake (5.24 ± 0.39 %ID/g) in melanoma tumour at 30 min post-injection, with high tumour-to-background contrast. The integrin α v ß 3 specificity of the tracer was corroborated by blocking study. Preliminary clinical studies in locally advanced breast cancer (LABC) patients indicated specifically high tumour uptake (SUV max 10-15) with good contrast. Conclusions: The present study successfully demonstrates the 'mix and use' approach in 68 Ga-radiopharmaceutical preparation for molecular imaging and also illustrates that expensive purification modules may not be required provided the chelator system is properly chosen.Moreover,this is one of the very few reports which presents preliminary clinical data on use of 68 Ga-NODAGA-(RGD) 2 .
Angiogenesis Imaging in Patients with Breast Carcinoma using PET based Ga-68 NODAGA RGD 2 : In-house preparation
Rakhee Vatsa, Jaya Shukla, Priya Bhusari, Sunil Kumar, 1 Gurpreet Singh, 2 Amanjit Bal, 3 Sudipta Chakraborty, 3 Ashutosh Dash, 4 Devinder Kumar Dhawan, Bhagwant Rai Mittal
Department of Nuclear Medicine and PET, 1 Surgery, 2 Histopathology, PGIMER, Chandigarh, 3 Isotope Applications and Radiopharmaceuticals Division, BARC, Mumbai, 4 Centre for Nuclear Medicine, Panjab University, Chandigarh, India
Background and Aim: Breast cancer accounts for one third of all cancers. Formation of new blood vessels is regulated by integrin α v ß 3, which are over expressed on various tumours like breast, lung and prostate carcinomas, melanomas and osteosarcomas. α v ß 3 integrins have sites for the binding of RGD (Arginine-Glycine-Aspartic acid) tripeptide. This study aims to image angiogenesis in breast carcinoma patients using Ga-68 NODAGA-RGD 2 and its correlation with microvessel density (MVD) data obtained from immunohistochemistry. Materials and Methods: Radiolabelling for NODAGA-RGD 2 was done in-house. Optimization of labelling was done at various temperatures, reaction time and pH with freshly eluted Ga-68. The characterization of purified Ga-68 NODAGA-RGD 2 was done by HPLC and MALDI-TOF mass spectrometry. Quality control parameters include Radio-ITLC, Gas chromatography, sterility and pyrogen testing. After obtaining ethical clearance from institutional ethics committee, locally advanced breast carcinoma patients (n=30, all female; mean age 51 years; range 29-75 years) were enrolled in this study and informed written consent was taken from all patients. Whole body acquisition was done on a dedicated PET-CT scanner with 90 sec per bed position, 45 min post intravenous administration of 111MBq-185MBq of Ga-68 NODAGA-RGD 2 . Anti-CD31 antibody was used for immunohistochemistry. CD31 stained vessels were counted at 40X magnification. Results: Preparation yield at RT was >94% with 40 µg peptide. However >95% radiolabelling yield was achieved by heating 20 µg peptide at 95ΊC for 5 and 10 min. The optimum pH for the reaction was 4.0. The RCP of pre-purified and purified Ga-68 NODAGA-RGD 2 was >90 and >99% as determined by ITLC. The residual ethanol content was below the permissible limit (4000 ppm) and was raging from 1946-2495 ppm in all samples. The endotoxins content was ranged between 1.2-3.7 EU/ml, indicating apyrogenic nature of prepared Ga-68 NODAGA-RGD 2 . Physiological uptake of radiotracer was seen in liver, spleen, ventricles, thyroid and salivary glands with excretion through the kidneys. Variable radiotracer uptake was noticed in breast lesion in patients with the SUVmax ranging from 2.89-21.12. Metastatic lesions were also detected. Tumour uptake was well correlated to microvessel density indicating the application of Ga-68 NODAGA-RGD 2 in imaging angiogenesis. Conclusion: Prepared Ga-68 NODAGA-RGD 2 is suitable for injection and showed good tumour to background ratio in carcinoma breast patients which is well correlated with MVD indicating the application of this radiotracer as a potential agent for imaging angiogenesis.
To Evaluate Role OfGa68-dotatate PET-CT For Radiation Therapy Planning in meningioma - Preliminary Workup
Atul Gada, Mahitha, Praveen, Giri P, Nani, Revathy, Suresh, Jyotsna Rao, Alka C, Kalyani Reddy, P Upadhayay, K Bhattacharya, Nanditha S, Roopesh K
Apollo Gleneagles PET-CT Centre and Department of Radiation Oncology, Jubilee Hills, Hyderabad, India
Background and Aim: To Evaluate Role Of Ga68-dotatate PET-CT For Radiation Therapy Planning in meningioma - Preliminary Workup
Materials and Methods: Human meningioma cell strongly express somatostatin receptor .we retrospectively analysed 27 patients data as to how far Ga68 dotatate pet-ct imaging is helpful to improve target volume delineation for radiotherapy planning compare to MRI. After validation of localization, volumetric accuracy and images registration Dicom images were transferred to radio therapy centre. 27 patients were scanned on flat bed with personalized rigid radiotherapy mould covering region of interest to prevent positioning differences. Data were exported to nucletron oncentra treatment planning contouring system. Target delineations were done using PET-CT data & spy Glass. After biological target and critical volume definition, data were sent to plato sunrise TPS for IMRT planning. Using dose volume histogram dose determined for tumors & critical organs. Plan is exported to Siemensprimus linac using lantis software for IMRT execution or using eclipse data were sent to Novalis Tx in some cases. Results and Conclusion: SRS imaging can be reliably used for tailoring radiation therapy planning.Technique allows better discrimination between SR2 expressing meningioma & tumor free tissue, more useful in skull base lesions. Radiation oncologist can better contour involved tumor volume with greater precision.PET provided additional information concerning tumor extension & planning target volume was modified in 50 % of cases.
Simultaneous Positron Emission Tomography-Magnetic Resonance Imaging with Gallium 68 Prostate-specific Membrane Antigen: Next footstep in Imaging of Recurrent Prostate Cancer-initial Results and preliminary experience.
Aashish Gambhir, Amarnath Jena, Sangeeta Taneja, Pradeep Negi
PET Suite, Department of Molecular Imaging and Nuclear Medicine, Indraprastha Apollo Hospital, Mathura Road, Sarita Vihar, New Delhi-76, India
Background and Aim: At present, Positron emission tomography (PET) combined with computed tomography (CT) is considered as the most accurate method of oncologic staging of recurrent prostate cancer. However PET/CT is marred by the limited soft tissue contrast of CT which may be overcome using a fully integrated, whole body simultaneous PET/MRI system combining high-resolution simultaneous morphologic and functional data. The purpose of this study was to assess the feasibility and the utility of whole body simultaneous 68Ga PSMA PET/MRI in restaging recurrent prostrate carcinoma. Materials and Methods: 12 patients with biopsy proven prostrate adenocarcinoma post-surgery, radiotherapy or hormonal therapy with raised serum PSA or clinical suspicion of recurrence underwent simultaneous PET/MRI using [68Ga] Ga-PSMA-HBED-CC tracer. Prostatic bed recurrent lesion, nodes and metastases were evaluated on PET, MRI and PET/MRI for lesion count and diagnostic confidence (DC). Histopathology, clinical/imaging follow-up served as the reference standard. Results : of 12 patients, 4 did not reveal any locoregional or distant metastatic disease on follow up; 5 showed features of local recurrence in prostatic bed, 3 had lymph nodal involvement with up to 16 distinct lymph nodal lesions and 2 had distant metastasis yielding more than 39 distinct bony, brain, hepatic and lung metastatic lesions. Fused PET-MRI showed highest diagnostic confidence score as compared to PET and MRI alone. Apart from distinctly detectable larger nodal and bone lesions, 68Ga-PSMA PET/MRI identified smaller metastases and small sized lymph nodal involvement. Conclusions : our preliminary results indicate possible incremental benefit of 68Ga-PSMA PET/MRI compared to MRI alone. 68Ga-PSMA PET/MRI shows promising potential in restaging men with biochemical failure post definitive treatment of prostate cancer.
Impact of PSMA PET Scan On Prostate Cancer Management
Department of Nuclear Medicine, Gujarat Imaging Centre, Samved Hospital, Ahmedabad, India
Background: Conventional imaging in prostate cancer has significant limitations in the diagnosis, especially in early and recurrent disease. It is also difficult to differentiate indolent from aggressive disease. PSMA is a type 2 membrane glycoprotein which is over expressed in prostate cancer. The expression increased with tumour aggressiveness, disease recurrence, metastatic disease and androgen independence. It differentiates between malignant and benign prostate issues. 68 Ga-PSMA scan can reliable detect prostate cancer relapses and metastases with high contrast at low PSA levels. Aim: Ga-68 PSMA scan is used for accurate staging of primary disease, restaging of recurrent disease and evaluation of metastases. The aim was to study the impact of PSMA scan in all three scenarios in 18 patients, to know if treatment plans were changed. Materials and Methods: Eighteen patients with histologically proven prostate cancer underwent Ga-68 PSMA scan between October 2014 to March 2015. The age was from 54 to 82 (mean 64). PSA values were from 0.3 to 48 (mean 13.6). Gleason score was from 6 - 9. 11 (61%) patients were primary untreated cases while 7 (39%) patient were treated with surgery (3 patients), surgery with radiotherapy (3 patients) and hormonal therapy (1 patient). All patients underwent an abdominal CT scan or MRI and a Tc MDP bone scan. Based on this imaging treatment was planned. Then all patients underwent a PSMA scan within. Results: PSMA scan showed no disease in 1 patient, loco regional disease in 6 patients and metastatic disease in 11 patients. A total of 46 lesions were detected - 1 local recurrence, 3 primary prostate lesions, 9 nodal lesions and 33 bone metastases. MDP bone scan showed 12 lesions in 3 patients and 8 suspicious lesions, 13 more lesions were detected on PSMA PET scan. PSMA PET changed the treatment plan in 8 patients (44%). Of these 5 (62%) were up staged from local to metastatic disease and treatment was changed from local to hormonal therapy. 1 patient - patient 12 - preferred hormonal therapy in view of low PSA and single positive site. Conclusion: Ga 68 PSMA PET scan significantly influence management of prostate cancer in all stages. While it is useful in early primary disease and high volume, metastatic disease, it is most useful in lower PSA ranges, especially in biochemical relapse after primary therapy. 68Ga PSMA PET-CT scan has a sensitivity of 83.8% at PSA lesser than 2.2 ng/ml. It can be used as single imaging modality for treatment planning.
Incidence of below knee skeletal metastases on 18 F-NaF PET CT - can we obviate the need for whole body acquisition?
KA Shaha, NC Purandare, S Shah, A Agrawal, V Rangarajan
Department of Nuclear Medicine and Molecular Imaging, Tata Memorial Hospital, Mumbai, India
Background: Skeleton is common site of metastases in cancers. 99m Tc-MDP bone scan and 18 F-NaF PET/CT are done for skeletal metastatic workup in cancer patients. 18 F-NaF PET/CT scan is preferred because of favourable pharmacokinetics and superior imaging qualities. The routine acquisition in oncologic PET/CT especially 18 F-FDG PET/CT is from eyes to thighs because of very low incidence of below knee metastatic disease. Considering this observation we decided to test if the same extent of acquisition can be sufficient and applicable for 18 F-NaF PET/CT scans. Hence we performed retrospective audit of 18 F-NaF PET/CT scans referred to our department for metastatic work up. Aim: Of study was 1) to calculate the incidence of skeletal metastasis below the knee in cancer patients.2) to assess, whether we can obviate the need to perform whole body acquisition from vertex to toes. Materials and Methods: A total of 587 consecutive 18 F-NaF PET/CT scans were retrospectively analysed by panel of two nuclear physicians and one radiologist for incidence of below knee metastases. The scans were interpreted as metastatic or non-metastatic with below knee metastases present or absent. Bone and soft tissue tumours were excluded as most of them are extremity tumours. Results: Patient population consisted of breast 51.44% (302), prostate 20.61% (121), lung 2.72% (16), thyroid 1.02% (6), HCC 6.64% (39), genitourinary 11.07% (65), gastrointestinal cancers 2.72% (16) and others 3.74% (22). 272 (46.3%) were treatment naive and 315 (53.7%) were imaged after treatment. Out of 272 treatment naive scans, 76 (27%) were metastatic with below knee metastases seen in 6 (2%). 5 of them had multiple skeletal metastases and 1 was solitary exclusively below knee metastasis. Out of 315 post treatment scans, 147 (47%) were metastatic with below knee metastases seen in 14 (4%). Overall incidence of metastases was 37% with below knee metastases in 3%. Of the entire patient population only 1 patient (0.17%) showed exclusively below knee skeletal metastasis. Conclusions: 1)Though overall incidence of skeletal metastases below knee was low (3%), the incidence of exclusive below knee metastases is extremely low (0.17%). 2) Scan acquisition from vertex to knee yields same information as that of vertex to toes. 3) Thus whole body scan acquisition can be obviated and limited from vertex to the knees. 4) This will lead to reduced scan times thereby increase the patient comfort, reduce radiation exposure from the CT and provide more machine time for other studies in high volume centres.
68 Ga-PSMA-HBED-CC PET-CT imaging in the evaluation of prostate cancer and its impact on management: Preliminary analysis of one hundred patients
Arun Sasikumar, Ajith Joy, Raviteja Nanabala, M. R. A. Pillai
DDNMRC PET Scans, KIMS Pinnacle, Trivandrum, Kerala
Background and Aim: Prostate cancer (PCa) is the most common cancer and second most common cause of cancer deaths among men. PET-CT imaging based on the novel radiopharmaceutical, 68 Ga-PSMA-HBED-CC ( 68 Ga-PSMA) is emerging as an ideal tool for the accurate assessment of disease status in patients. Materials and Methods : 100 patients referred for 68 Ga-PSMA PET-CT imaging were included in the study. All patients underwent 68 Ga-PSMA PET-CT imaging after injection of a standard dose of 68 Ga-PSMA prepared in-house. PET-CT scan was done on a Siemens Biograph 6 True Point PET-CT machine. Results: 100 males with a median age of 69 years (Range: 37-90yrs) with a diagnosis or clinical suspicion of prostate cancer were included in this study. Average dose of 68 Ga-PSMA injected was 3.61mCi (Range: 2.95-5.57 mCi). All the images were interpretable and the lesions had excellent target to background ratio. 32 patients were referred with a clinical suspicion of prostate cancer and a median PSA value of 11.6ng/ml (Range: 0.96 to 4156ng/ml). 16 patients had a focal intense uptake in the prostate gland suggestive of prostate carcinoma. 16 patients had no abnormal focal tracer uptake in the prostate gland, hence prostate biopsy was avoided and put on clinical follow up. 24 patients with PCa (Gleason scare ranging from 6-10) were referred for initial staging. The median PSA value was 29.15 ng/ml (Range: 1.3-100). 23/24 patients had intense tracer uptake in one or more areas of the prostate gland. Nine patients had pelvic lymph nodal metastases, and three patients had abdominal lymph nodal metastases. Among these three patients one had additional skeletal metastases, one patient had extensive mediastinal and skeletal metastases and one patient had visceral metastasis (Adrenal). One patient had isolated skeletal metastasis.44 patients of prostate cancer were referred following some form of therapy with clinical suspicion of recurrence / biochemical recurrence. The median PSA value was 6.2ng/ml (Range: 0.06 to 906). In 40/44 (90.9%) patients, site of disease involvement could be detected. 26 out of 44 cases have local recurrence in the prostate gland or the prostatic bed. 21 out of 44 cases had regional pelvic lymph nodal metastases. Six patients had abdominal lymph nodal metastases and four of them had mediastinal lymph nodal metastases also. 21 out of 44 cases had skeletal metastases. One patient had extensive disease. Conclusions: 68 Ga- PSMA PET-CT is very useful imaging tool in lesion characterization, initial staging and recurrence/restaging of PCa.
PSMA PET/CT in evaluation of primary prostate cancer: Experience from a tertiary care centre in India
Akshay Kumar, Promila Pankaj, Ritu Verma, Anjali Jain, Ethel S. Belho, Harsh Mahajan
Department of Nuclear Medicine and PET CT, Mahajan Imaging Centre, and Ganga Ram Institute for Postgraduate Medical Education and Research (GRIPMER), Sir Ganga Ram Hospital, New Delhi - 110 060, India
Background : Adenocarcinoma of prostate is the second most common cause of cancer death among men. Prostate-specific membrane antigen (PSMA) represents a cell surface target suitable for imaging metastatic lesions as it is expressed by nearly all prostate cancer cells with enhanced expression levels in poorly differentiated, metastatic, and hormone-refractory carcinomas. Recently labelling procedures have been developed to label PSMA ligands with 68 Gallium ( 68 Ga) which makes them suitable for PET imaging. Aim : To evaluate the role of Ga-68 PSMA PET/CT in evaluation of primary prostate cancer. Materials and Methods : Total 344 patients underwent Ga-68 PSMA PET/CT study in our department for various indications between March 2014 and August 2015. Out of them eighty eight patients (n =88) mean age 70.27+/- 5.56 ranging from 44 to 84 years, with suspected primary prostate cancer, who underwent Ga-68 PSMA PET/CT scan as part of staging work up were evaluated retrospectively. All the patients underwent prostate biopsy within two weeks of the scan. Size and SUVmax of the evident prostatic lesion on Ga-68 PSMA PET/CT scans were measured and SUVmax > 3 was considered as criteria for PET positivity. Histopathological analysis of biopsy specimen was considered as reference standard for the diagnosis of the prostate cancer. Scan parameters were correlated with histopathological report and various parameters like sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV) and accuracy of Ga-68 PSMA PET/CT were calculated. Results : The sensitivity, specificity, PPV, NPV and accuracy of Ga-68 PSMA PET CT for the detection of primary prostate cancer were 96%, 50%, 88%, 75% & 87% respectively. The median SUVmax of primary lesion in biopsy proven subjects was 6.5, which was significantly higher than the mean SUVmax obtained in biopsy negative subjects was 2.8. However, the study failed to find any significant correlation between SUVmax of the primary lesion and Gleason's score (r=0.007) & PSA levels(r=0.17). Ga-68 PSMA scan identified additional bony and visceral (lung & liver) metastasis in 19 cases. Conclusion : Our preliminary experience suggests that Ga-68 PSMA PET/CT scan is a good modality for evaluation of primary prostate cancer, correlating well with histopathological analysis and finding additional sites of metastasis, thereby guiding their overall clinical management.
Does SPECT/CT offer incremental benefit over planar lympho-scintigraphy in sentinel node biopsies in oral cavity squamous cell carcinomas?
Piyush Chandra 1 , Sanket Dhake 1 , Archi Agrawal 1 , Sneha Shah 1 , Nilendu Purandare 1 , V. Rangarajan 1 Sourav Dutta 2 , P. Chaturvedi 2
1 Department of Nuclear Medicine and Molecular Imaging, Tata Memorial Hospital, 2 Head/Neck disease management group, Tata Memorial Hospital, Mumbai, India
Background and Aim: Sentinel Node biopsy (SNB) is increasingly being recognized as an alternative to elective Neck Dissection (END), for management of clinically node negative neck in oral squamous cell cancers (SCC). Adding SPECT/CT to planar lymphoscintigraphy (PL) pre-operative lymphatic mapping with leads to identification of nodes not visualized on PL and better anatomical localization, thereby aiding the surgical plan. This fact is validated in melanoma, breast and pelvic malignancies in recently concluded multi-centric study by IAEA. Our aim was to assess whether SPECT/CT offers incremental value over PL alone in detection of sentinel nodes in oral SCC. Materials and Methods: This is a retrospective analysis of 44 patients with clinically node negative oral cavity SCC who underwent sentinel node biopsy and END (level I-IV). 99mTc-labelled Human Serum Albumin Nanocolloid (0.5-1.0 ml) was injected at 2-4 sites on the edge of the tumour 3-6 hours before surgery. Static lymphoscintigraphy in two planes (anterior and lateral) followed by SPECT/CT (low mA) was done. Using intra-op gamma probe, up to three hot nodes was harvested from each neck. Histo-pathology of END served as standard of reference. Results: The cohort consisted of 37 males and 7 females with mean age of 46 (range 29-70). Site of primary disease was oral tongue 91% (n=40) and buccal mucosa 9% (n=4). Histopathology of END revealed occult nodal disease present 29.5% (n=13) patients. Sensitivity, Specificity, NPV and PPV of SNB was 76%, 100%, 91% and 100 % respectively. A total of 183 sentinel nodes, with a mean of 8.13 per patient. PL and SPECT revealed hot spots in the ipsi-lateral neck in 95% (n=42) patients and 9% (n=4) in contra-lateral neck. PL revealed 77 hotspots with a mean of 1.75 per patient and SPECT revealed 92 hotspots with a mean of 2.5 per patient. Additional hotpots were identified in 8 patients on SPECT/CT, including 3 patients, where PL didn't detect any nodes. In 2 patients, both PL and SPECT were negative. The detection rate by PL, SPECT, and gamma probe was 93, 95 and 97% respectively. Good concordance was seen with anatomical localization on SPECT/CT and gamma probe findings. Conclusion: SPECT/CT in sentinel node biopsies in oral cavity SCC, allows better anatomical characterization and detects more number of sentinel nodes than planar lymphoscintigraphy alone. Integrated diagnostic CT might further increase the spatial resolution of SPECT and hence detectability of occult nodal metastasis. Given the excellent accuracy of combined planar imaging and intra-op gamma probe, SPECT/CT, however, is not clearly advantageous.
Comparison of 68 Ga PSMA PET/CT and 18 F- NaF PET/CT in evaluation of skeletal metastases in Prostate Cancer
Aravintho N, Agrawal A, Bakshi G, Purandare N, Murthy V, Kabnurkar R, Shah S, Rangarajan V
Department of Nuclear Medicine and Molecular Imaging, Tata Memorial Hospital, Parel, Mumbai, India
Background and Aim: The expression of prostate-specific membrane antigen (PSMA) is increased in prostate cancer. Recently, Ga68-PSMA (Glu-NH-CONH-Lys-(Ahx)-[68Ga(HBED-CC)]) was developed as a ligand which exhibits a high target-to-background ratio and a high specific internalization property. The aim of this study was to compare finding of 68 Ga PSMA PET/CT with 18 F-NaF PET/CT in evaluation of skeletal metastases. Materials and Methods :100 consecutive patients with carcinoma prostate who underwent 68 Ga-PSMA PET/CT and 18 F-NaF PET/CT at baseline evaluation (n=38) and following biochemical recurrence or disease progression (n=62) were retrospectively analysed.Uptake of 68Ga-PSMA in skeletal system significantly higher than background was considered positive for metastasis. 68 Ga-PSMA and NaF PET/CT scans were visually analysed to look for skeletal lesions. Increased uptake on NaF with characteristic findings of skeletal metastases on CT was used to consider them as positive lesions. Results: Mean age of the population was 66 years, mean Gleason's score was 8.2 and median serum PSA was 28 ng/ml. Both the scans were negative for skeletal metastases in 36 (36%) patients and positive for metastases in either of the scan in 64 (64%) patients. Both scans revealed equal number of lesions in 41 patients leading to total 77 concordant result and 23 discordant result. Among the discordant result, 9 were baseline evaluation and 14 biochemical recurrence or suspected disease progression.NaF revealed more lesions in 18 patients (4 initial and 14 biochemical recurrence or suspected disease progression). PSMA detected more number of lesions in 5 patients in the initial staging group and none in the post treatment setting. Our results show that though 18 F-NaF PET/CT revealed more lesions in 14 patients in the post-treatment setting which were negative on PSMA, it is likely that this could be due to post treatment healing changes. In the setting of initial evaluation, more lesions were detected by PSMA in 5patients and by NaF in 4 patients. In this group our numbers are too small to accurately comment which tracer would be more appropriate. Conclusion: Both NaF and PSMA are good tracers for evaluation of skeletal metastases in prostate cancer. However the lack of PSMA avidity in the post treatment setting opens up a new avenue for response assessment of skeletal metastases. In initial evaluation, though marginal superiority of PSMA was seen over NaF in detection of skeletal lesions, larger studies with more number of patients will be needed to conclude the superiority of one over the other.
Utility of 18F-FDG PET/CT in the evaluation of histologically proven cases of ocular adnexal lymphoma (OAL)
Thanseer NTK, Padinhare Keloth, Arun Kumar Reddy Gorla, Rajender Kumar Basher, Ashwani Sood, Anish Bhattacharya, Bhagwant Rai Mittal
Department of Nuclear Medicine and PET, Post Graduate Institute of Medical Education and Research, Chandigarh - 160 012, India
Background: Ocular adnexal lymphomas (OAL) are uncommon disease entities, majority of which are extra nodal non-Hodgkin lymphomas (ENHL). ENHL are conventionally staged with Ann Arbors system, which ideally doesn't serve the desired prognostic stratification. The latest AJCC staging system proposed an entirely discrete staging system for OAL to address these limitations. Also, there is limited literature available regarding the evaluation of OAL with FDG PET/CT. Aim: The objective of the present study is to evaluate the clinical utility of 18F FDG PET/CT in patients with histologically proven OAL. Materials and Methods : We retrospectively evaluated the data of histopathologically proven cases of OAL subjected to PET/CT for initial staging, response assessment, recurrence evaluation and disease surveillance. All the patients underwent 18 F-FDG PET/CT as per the standard departmental imaging protocol. PET /CT findings were evaluated separately by two experienced nuclear medicine physicians. Results: A total of 35 PET/CT studies in 15 patients (9 males & 6 females; age range 20-75 years; mean age 54.6 years) were included for analysis. All the cases were of non-Hodgkin Lymphoma and most common histological subtype was extranodal marginal zone lymphoma (ENMZL) of MALT type 46.6% (7/15) followed by follicular lymphoma 26.6% (4/15), DLBCL 13.3% (2/15) and mantle cell lymphoma 13.3% (2/15). Of the 13 studies performed for initial staging, orbital involvement was detected in only 10 patients; local extra orbital involvement in 6 patients (periosteum 4, sinuses 2 and intracranial 2); lymph node sites (regional 6, distant 8); systemic involvement in 5 patients (marrow 3, spleen 1, pleura 1). Additional sites that upstaged the disease (compared to CT) were noted in 38 % patients (5/13; 2 distant nodes, 2 marrow and 1 pleural). Among the 13 studies for response assessment, residual FDG uptake was noted in the in 6 patients (orbits-3 and mediastinal nodes- 3 with inflammatory pattern). All the patients with mediastinal nodes were asymptomatic and only one patient with orbital uptake had recurrence on follow up. Of the 7 studies with suspected clinical recurrence, FDG PET/CT was positive in 3 patients (1 local recurrence and 2 with systemic nodal disease). No abnormal FDG uptake was noted in 2 studies performed for surveillance and found to be normal on follow up. Conclusion : Although physiologic FDG uptake in the orbital tissues and low volume nature of the lymphomatous orbital deposits limits the performance of FDG PET/CT, its ability to identify additional sites of systemic lymphomatous involvement affects the staging and thus the management of significant number of patients with OAL.
16α-(18) F-Fluoro-17ß-Estradiol ((18) F-FES) PET/CT and 2-deoxy-2-[fluorine-18] fluoro-D-glucose ( 18 F-FDG) PET/CT in Breast Cancer Patients
Arpana Arbind, Nikhil Seniaray, Harshul Sharma,
Abhinav Jaimini, Maria D'Souza, Santosh Pandey,
1 Anupama Dutta, 2 AK Mishra, Anupam Mondal, Rajnish Sharma
Department of PET Imaging, Institute of Nuclear Medicine and Allied Sciences, New Delhi, 1 Division of Cyclotron and Radiopharmaceutical Science, Institute of Nuclear Medicine and Allied Sciences, New Delhi, India
Background and Aim: Majority of breast cancer expresses oestrogen receptor (ER) in primary lesions or in metastatic sites, which have good prognosis on endocrine therapy than ER negative breast cancers. So, it is of paramount importance to know the ER status in primary tumour and in metastatic sites. ER status is primarily determined by immunohistochemical staining methods on biopsy materials whereas; FES-PET/CT is unique method to determine the molecular information of functional ER expression non-invasively for the whole body basis. The aim of this study is to find out the role of (18F) FES PET/CT in whole body status for biopsy proven breast cancer patients. Materials and Methods: Seven patients of biopsy proven breast cancer were subjected to both WB (18F) FES and FDG PET/CT in our centre. Informed written consents were taken from each patient. Around 222MBq of FES and 370 MBq of FDG were injected intravenously on different days and after approximately 60 minute on respective days, WB PET/CT was taken using GE Discovery STE PET CT camera. Results: One patient out of the seven, had shown increased tracer both FES and FDG uptake in primary lesion without any other metastasis. Among them, three patients, who were post operated, post chemotherapy and post radiotherapy with biopsy proven carcinoma breast and having positive ER status of primary lesion, came to find out reoccurrence of tumour. Her FES PET/CT and FDG PET/CT both showed increased tracer uptake at multiple lesions. And other three patients, who were also post operated, post chemotherapy and post radiotherapy carcinoma breast, had shown no abnormal increase in FES uptake while abnormal increase in FDG uptake in multiple lesions in their PET/CT. Conclusion: Both FDG and FES-PET/CT as a baseline scans helps to decide further endocrine treatment strategies. The patients showing increased FES uptake in metastatic sites or in primary lesions are more likely to benefit by endocrine therapy. Patients, showing no abnormality in FES-PET/CT, are not required to go for endocrine therapy, however false negative results due to various factors, should always be considered. The correlative FES-PET/CT provide the functional ER status of breast cancer patients on whole body basis and helps in determining the efficacy and response from endocrine therapy more accurately than any other pathological assessments and it also helps in deciding whether to switch or not for any other therapeutic strategy in case of resistance to therapy.
Sentinel Lymph Node mapping in Carcinoma Penis and malignant melanoma - Cancer Institute experience (W.I.A)
N. Parvathinathan 1 , S. Lavanya 1 , N. Anandi 1 ,
G. K. Rangarajan 1 , Balkis Begum 1 , R. KrishnaKumar 1 , Sivakumar 2 , Anandhraja 3 , Shirley Sundersingh 4
1 Deptartment of Nuclear Medicine, 2 Assistant professor of Surgical Oncology, 3 Associate professor of Surgical Oncology, 4 Professor and HOD, Oncopathology, Cancer Institute (W.I.A) Chennai, Tamil Nadu, India
Background and Aim: We routinely do sentinel node biopsy for Ca. penis and extremity melanoma patients who are clinically node negative. We hereby report our experience in 31 patients for whom SLNB procedure has been done in the past 1 year in our institute. Materials and Methods: Sentinel Lymph Node Biopsy (SLNB) is done for Ca. penis and extremity melanoma patients without clinically palpable regional nodes. 31 Patients were taken up for this study. Tc99m Sulphur Colloid was prepared as per norms of BRIT, Mumbai and was injected subcutaneously around the lesion. Imaging was done after 90 minutes to 120 minutes. If the regional lymph node is visible, the lower most node is marked and the patient is shifted to operation theatre. Blue dye was injected in the lesion. Incision was done after 5minutes. Nodes having 10 times the background counts and Blue dye concentration were removed. The removed nodes were submitted for frozen section studies. Results: We have done 31 SLNB procedures in past one year. Out of whom 29 patients are Ca.penis and 2 are melanoma of the foot. Out of 31 patients, 3 had (1 melanoma and 2 penis) had frozen section proved positive nodes. Then we proceeded with the regional block dissection. Post operatively patients were closely followed up for a period of 6 to 9 months. So far SLNB negative patients have not developed any nodal recurrence. Conclusion: Lymphoscintigraphy with Sulphur colloid is highly sensitive in localization of sentinel node. SLNB procedure is very useful in patients for whom unnecessary nodal dissections are avoided and the associated morbidity prevented.
Innovative exposure reductive technique of high dose F18 FDG pack dispensing
V. V. S. Prabhakar Rao, P. Hemalatha, V. Naveen Kumar, MD. Azhar, Ch. Mohana Vamsy
Department of Nuclear Medicine & PETCT, Omega Hospitals, Hyderabad, India
Background and Aim : To reduce the radiation exposure doses to the nuclear medicine professionals handling high doses of F18-FDG. Materials and Methods: Materials include: 1. 18 G Lumbar puncture needle, 2. 18 G Injection needle, 3. Three way connector, 4. Improvised lead pot with openings on both ends. Methods included: Improvised innovative F18 - FDG Pack Safe Dispensing Technique F18 - FDG packs supplied from the cyclotrons usually contain high amounts of radioactivity ranging from 150-200 mCi. Dispensing and administering such high amounts multiple times to patient's results in high exposure to the radiation professionals. Current practice of direct withdrawal from the master vial is cumbersome, time consuming and may lead to spillage and needle prick injuries. To contain this exposure an innovative technique has been devised in our institute. The master vial is placed in the tungsten vial pig and its cap closed. An 18G injection needle inserted as a vent. Lumbar puncture needle is inserted till the bottom of the vial. A three way is connected to the LP needle hub. The open ended smaller lead container is threaded over them. The three way hub brought out of the other end. Sterile normal saline is attached to one hub. The desired activity is drawn alternatively from activity vial and saline flush manipulating the three way cock. Results: This technique and manoeuvre resulted in withdrawal of precise volumes of FDG from the master vial multiple times, faster, safer and spillage free. The annual dose exposure dose to our personnel has drastically reduced with this technique. Conclusion: This technique once practiced results in drastic decrease of the TLD readings, thus achieving the world-wide ALARA principle of the radiation safety.
177 Lu-CHX-A''-DTPA-Bevacizumab: A potential radioimmunotherapeutic agent for cancer
Mythili Kameswaran a , Usha Pandey a , Naresh Gamre a , K. V. Vimalnath a , H. D. Sarma b , Ashutosh Dash a
a Isotope Production and Applications Division, b Radiation Biology and Health Sciences Division, Bhabha Atomic Research Centre, Trombay, Mumbai - 400 085, India
Background and Aim: Angiogenesis has become the target of therapeutic approaches in oncology. Amongst the complex system of pro and anti-angiogenic factors, the Vascular Endothelial Growth Factor (VEGF) system is the key mediator of tumor-initiated angiogenesis and is therefore target of anti-angiogenesis agents. Bevacizumab (Avastin), a humanized MoAb which inhibits VEGF-A, is the first anti-angiogenic agent approved by US FDA in the first-line treatment of metastatic colorectal cancer. The objective of this study was to explore the potential of 177 Lu-CHX-A''-DTPA-Bevacizumab as a radioimmunotherapeutic agent that would provide insights into the angiogenic stimulus and in the treatment of VEGF expressing tumours. Materials and Methods: Bevacizumab was conjugated with paraisothiocyanatobenzyl cyclohexyl diethylenetriamine pentaacetic acid (p-NCS-Bn-CHX-A''-DTPA) and subsequently radiolabelled with 177 Lu. The radioimmunoconjugatewas purified using a Sephadex G-25 column and characterized by HPLC using a gel column. In vitro stability of the radioimmunoconjugate was determined up to 7 days post preparation. Biodistribution studies in C57BL6 mice bearing melanoma were carried out at various time points up to 96 h post injection to determine the uptake of the 177 Lu-CHX-A''-DTPA-Bevacizumab by the tumour. Specificity towards VEGF was determined by inhibition studies wherein cold Bevacizumab was co-administered with the tracer prior to biodistribution studies. Results: The radiochemical purity (RCP) of 177 Lu-CHX-A''-DTPA-Bevacizumab was > 98%. In the standardized HPLC system, 177 Lu-CHX-A''-DTPA-Bevacizumab had a retention time (R t ) of 14.4 minutes while free 177 Lu had R t = 21.0 minutes. The radioimmunoconjugate exhibited good stability in saline up to 7 days post preparation, when stored at 37°C. Uptake of the radioimmunoconjugate in the tumour of animals injected only with 177 Lu-CHX-A'-DTPA-Bevacizumab was significant (~ 20.5 % ID/g at 24 h) which reduced to ~11.7 % ID/g in the animals co-injected with cold Bevacizumab. The decrease of ~ 43 % in tumour uptake in presence of the cold antibody confirmed the specificity of 177 Lu-CHX-A'-DTPA-Bevacizumab towards VEGF. Conclusions: The 177 Lu-CHX-A''-DTPA-Bevacizumab conjugate with a radiochemical purity of > 98% exhibited excellent stability when stored at 37°C up to 7 days post preparation. Bio distribution studies in melanoma bearing C57BL6 mice showed good uptake and specificity for VEGF indicating its potential for further evaluation as a radioimmunotherapeutic agent for various cancers over-expressing VEGF.
In-vitro cell uptake studies of new 99m Tc-4+1 analogue of 131 I-mIBG for Neuroendocrine tumor imaging
Shubhangi Mirapurkar, Shalaka P, N. C. Joseph, Anupam Mathur, S. S. Sachdev
Board of Radiation and Isotope Technology, Mumbai, India
Background and Aim: Radio-iodine ( 123 I/ 131 I) labelled meta-Iodobenzylguanidine (mIBG) is an accepted radiopharmaceutical used for diagnosis of neuroendocrine tumours related to neural crest origin. However, restricted availability of 123 I produced from high energy cyclotron and non-ideal nuclear characteristics of 131 I for diagnostic applications necessitate the need for a rationale substitute. In the present work, an attempt has been made to synthesize a 99m Tc analogue of mIBG using '4+1' labelling approach and subsequently evaluating its efficacy for the aforementioned application. Materials and Methods: A guanidine derivative bearing an isonitrile group ('1') at the meta position suitable for 99m Tc labelling via 99m Tc-'4+1' strategy was synthesized in a three step synthetic procedure. This derivative was then radiolabelled with 99m Tc following the established 99m Tc-'4+1' labelling approach and characterized by HPLC. HPLC purified 99m Tc-'4+1' complex was then evaluated in neuroblastoma cell lines SK-N-SH and IMR-32 and results obtained were compared with no-carrier added- 125 I-mIBG (nca- 125 I-mIBG). Results: The desired derivative '1' was synthesized in an overall yield of 60%. The radiolabelled product was obtained in 85% yield and purity as characterized by HPLC. The cell uptake studies in SK-N-SH and IMR-32 cell lines showed uptake similar to nca- 125 I-mIBG and via active transport mechanism. This transport was specific as the uptake reduced with desmethylimipramine blocking. Conclusion: The in vitroneuroblastoma cell uptake studies exhibited efficacy of the 99m Tc complex for the NET transporter. Further evaluation in tumour xenografts is essential for concluding the potential of 99m Tc-4+1 complex in vivo.
Preparation of the Gastrin Releasing Peptide Receptor targeted radiopharmaceutical 177 Lu-AMBA using freeze-dried kits and its bioevaluation in prostate tumor model
Usha Pandey 1 , Archana Mukherjee 1 , Naresh Gamre 1 , K.V. Vimalnath 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, India
Background and Aim: Human cancers such as that of prostate and breast over-express Gastrin Releasing Peptide Receptors (GRP-R) which can be specifically targeted using the peptide bombesin and its analogues. Bombesin analogues have been previously radiolabeled with radioisotopes such as 90 Y and 177 Lu for possible therapeutic use. One such analog AMBA (DOTA-G-(4-aminobenzoyl)-Gln-Trp-Ala-Val-Gly-His-Leu-Met-NH 2 ) radiolabeled with 177 Lu is already under clinical trials for prostate cancer therapy. This work was aimed at the formulation of cold kits of the peptide AMBA, it's radiolabeling with 177 Lu and its in vivo evaluation in Swiss mice and in nude nice bearing PC-3 (prostate) tumor towards its possible therapeutic use in prostate cancer. Materials and Methods: Single vial kits of AMBA peptide were formulated in 0.1 M sodium acetate. Radiolabeling with 177 Lu was carried out by addition of 177 Lu activity (~ 25-30 mCi) into the kit vial and incubating the reaction mixture for 15 minutes at 80·C. 177 Lu-AMBA was then characterized by HPLC. In vitro stability studies were carried out up to 4 days at room temperature. Pharmacokinetic studies were carried out in Swiss mice at 3 h and 24 h post-intravenous injection of 177 Lu-AMBA. Biodistribution studies were also carried out in nude mice bearing PC-3 tumor at 3 h p.i. of 177 Lu-AMBA. Results: Freeze driedkits of the bombesin analogue AMBA containing 50 µg of the peptide per kit vial could be successfully formulated in 0.1 M sodium acetate. Radiolabeling yields exceeding 95 % could be obtained on radiolabeling with ~ 25-30 mCi of 177 Lu, as confirmed by HPLC. The final product contained 20 mg of ascorbic acid to prevent radiolysis. 177 Lu-AMBA retained good in vitro stability when studied up to 4 days at room temperature. Pharmacokinetic studies carried out in Swiss mice showed that 177 Lu-AMBA had a very high pancreatic uptake at both 3 h and 24 h p.i. (15.1±1.4 %ID/g and 6.9±1.0 %ID/g respectively) which showed its specificity to GRP-R, as pancreas is known to express GRP-R. Activity in other non-target organs was negligible. The product had a good tumor uptake in PC-3 tumor bearing nude mice at 3 h p.i. (4.8±0.5 %ID/g). Apart from the pancreas (which expresses GRP-R) which exhibited high uptake (20.1±2.0 %ID/g), other organs had negligible resident activity.
Evaluation of the effect of chelate on the myocardial uptake characteristics of 68 Ga labeled fatty acids for their potential use in myocardial imaging
Akanksha Jain 1 , Usha Pandey 1 , Anupam Mathur 3 , 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, 3 Radiopharmaceuticals Program, Board of Radiation and Isotope Technology, Navi Mumbai - 400 703, India
Background and Aim: Development of 68 Ga labelled fatty acids, as substitutes for [11C]-Palmitate and SPECT tracer 123 I-beta-methyl-iodophenylpentadecanoic acid, for metabolic cardiac imaging is of immense interest in clinical settings. This is due to ease of availability of 68 Ga, a positron emitter, through a portable 68 Ge/ 68 Ga generator and its superiority over the SPECT tracer in carrying out dynamic PET imaging. Few efforts in this direction have been taken in the past but with limited clinical success. Present work explores one such effort where a long chain fatty acid viz. undecanoic acid was derivatized at the ω-terminal with several chelates, radiolabelled and evaluated for their potential in vivo. Materials and Methods: Three different fatty acid analogues were synthesized by conjugation of 11-aminoundecanoic acid with the isothiocyanate group of different bifunctional chelators namely p-SCN-Bn-DTPA (S-2-(4-isothiocyanatobenzyl)-diethylenetriamine pentaacetic acid), p-SCN-Bn-NOTA (S-2-(4-isothiocyanatobenzyl) 1,4,7-triazacyclononane 1,4,7-triacetic acid) and p-SCN-Bn-NODAGA (S-2-(4-isothiocyanatobenzyl)-1,4,7-triazacyclononane-1-glutaric acid-4,7-acetic acid) at pH ~ 9. They were then radiolabeled with 68 Ga in sodium acetate buffer (pH~3.5) at room temperature. Formation of the complexes was confirmed by HPLC characterization. Biodistribution studies of the synthesized 68 Ga-fatty acid conjugates were carried out in Swiss mice to assess their potential for myocardial imaging. In addition, myocardial metabolism of the complexes in Wistar rats was investigated by isolating the heart post-intravenous injection of the respective 68 Ga complex and analyzing it by HPLC. Results: The three fatty acid conjugates namely, DTPA-fatty acid, NOTA-fatty acid and NODAGA-fatty acid, were successfully synthesized in good yields and purities. All the three analogues were radiolabeled with 68 Ga in ≥ 95% yields. Preliminary biodistribution studies in Swiss mice showed highest myocardial uptake for 68 Ga-NOTA-fatty acid (7.4±2.8% ID/g at 2 min p.i.) in comparison to 68 Ga-NODAGA-fatty acid (3.8±0.6% ID/g) and 68 Ga-DTPA-fatty acid (1.3±0.5% ID/g). All the complexes cleared rapidly from non-target organs such as blood, lungs and muscle via the hepatic route. HPLC analyses of the extracts of the heart samples of rats showed transformation of the parent fatty acid complex peak in all the three complexes. Conclusions: Synthetic modification of the fatty acid analogue through the NOTA chelate effected the maximal myocardial uptake among the three 68 Ga labelled 11C-fatty acid complexes. All three complexes showed signs of metabolic transformation in the myocardium, thereby favouring the synthetic design from clinical perspective. Efforts are underway to characterize the metabolites produced and evaluate several chain lengths of fatty acids using the chelator NOTA in order to achieve the highest myocardial/non-target ratios.
Production of 170 Tm suitable for clinical use for bone pain palliation in nuclear reactor: Crucial role of irradiation parameters
Mohammed Sahiralamkhan, Sudipta Chakraborty, Rubel Chakravarty, Ashutosh Dash 1
1 Isotope Production and Applications Division, Bhabha Atomic Research Centre, Trombay, Mumbai - 400 085, India
Background and Aim: Thulium-170 [t = 128.4 days, E (ß max) = 968 keV, Eγ = 84.3 keV (3.26%)] is an emerging therapeutic radioisotope having good potential for use in metastatic bone pain palliation (MBPP) as a cost-effective alternative to 89 Sr. While thermal neutron activation of natural Tm 2 O 3 is the convenient strategy for large-scale production of 170 Tm, the coproduction of 171 Tm (T = 1.92 y) could emerge as an impedimenttowards its clinical utility as a cost-effective alternative to 89 Sr. The present study is aimed towards establishing an optimized production strategy to obtain 170 Tm with adequate specific activity and radionuclidic purity in a medium flux research reactor. Materials and Methods: Activities of 170 Tm and 171 Tm produced by neutron irradiation of 169 Tm target at different neutron flux and for different irradiation times were theoretically calculated in order to arrive at the optimum conditions that will provide 170 Tmwith minimum 171 Tm impurity, while ensuring its specific activity adequate for clinical use. Based on the theoretical data, 170 Tm was produced by thermal neutron bombardment on natural Tm 2 O 3 (100% in 169 Tm) target. The irradiated target was dissolved in 0.1 M suprapure HCl to obtain 170 TmCl 3 solution. Yield and radionuclidic purity were assayed by gamma ray spectrometry. 170 Tm-EDTMP complex was formulated at hospital radiopahrmacy by adding ~370 MBq activity of 170 Tm into EDTMP kit containing 35 mg EDTMP, commercially available from BRIT. Preliminary clinical investigation of 170 Tm - EDTMP was carried out by assessing the distribution pattern of the preparation in a human patent with disseminated skeletal metastases. Results: It was found both from theoretical calculations and experimental results that, when irradiations were carried out at 5 × 10 13 n. cm -2 . s -1 for 14 d, the specific activity of 170 Tm and the level of radionuclidic impurity ( 171 Tm) present were 1.52 ± 0.01 GBq/mg and 0.08 ± 0.01 % respectively. Irradiation at higher neutron flux and for prolonged duration significantly enhances the 171 Tm impurity burden and eventually renders 170 TmCl 3 radiochemical not suitable for radiopharmaceutical preparation. 170 Tm - EDTMP was formulated at hospital radiopharmacy with ~99% radiochemical purity using 170 TmCl 3 produced. Preliminary clinical investigation showed site specific localization of the radiopharmaceutical in skeleton with preferential accumulation in metastatic lesion sites almost similar to 99m Tc-MDP scan. Conclusion: The goal of developing a viable strategy for large-scale production of 169Tm(n, γ)170 Tm with high radionuclidic purity and acceptable specific activity for use in bone pain palliation has been successfully accomplished by careful optimization of irradiation parameters.
Potential of 99m Tc carbonyl-DTPA-Rituximab as a tracer for sentinel lymph node detection
Mythili Kameswaran, Suresh Subramanian, Usha Pandey, Grace Samuel, Ashutosh Dash
Isotope Production and Applications Division, Bhabha Atomic Research Centre, Trombay, Mumbai - 400 085, India
Background and Aim: Preliminary work with 99m Tc carbonyl-DTPA-Rituximab was attempted to test its feasibility as a sentinel lymph node (SLN) tracer for patients with breast cancer. Detection of metastatic involvement of lymph nodesis important for management and prognostic evaluation in patients with breastcancer and recent reports indicate that sentinel node biopsy might influence treatment decisions especially in clinically node-negative patients with primary breast lymphoma. Materials and Methods: Rituximab was conjugated with p-NCS-Bn-DTPA and subsequently radiolabelled with 99m Tc via the 99m Tc carbonyl synthon. The radioimmunoconjugate was purified using a PD-10 column and characterized by HPLC using a gel column. In vitro binding and inhibition of the 99m Tc carbonyl-DTPA-Rituximab were carried out in normal lymphocytes and malignant cells (Raji) to demonstrate the specific binding of 99m Tc carbonyl-DTPA-Rituximab to lymphocytes. Studies of in vivo distribution and pharmacokinetics of 99m Tc-carbonyl-DTPA-Rituximab were performed in Wistar rat footpad model wherein the popliteal node serves as the sentinel lymph node. Passage of the radiotracer from the footpad injection site into the popliteal node and further on into non-specific regions was determined as a measure of its suitability for use in SLN detection. Results: Number of DTPA molecules attached per molecule of Rituximab was determined to be five. The radiochemical purity (RCP) of 99m Tc carbonyl-DTPA-Rituximab was > 95%. In the standardized HPLC system, 99m Tc carbonyl-DTPA-Rituximab had a retention time (R t ) of 14.0 minutes while free 99m Tc carbonylhad R t = 21.0 minutes. In vitro cell binding studies with 99m Tc carbonyl-DTPA-Rituximab in Raji cells showed a specific binding of 20±0.23% while studies in PBL showed binding of 11.9±0.42% indicating the presence of more CD20 receptors on the surface of malignant cells as compared to normal cells. Inhibition studies with cold Rituximab further confirmed the specificity of the radioconjugate. Significant uptake of 99m Tc carbonyl-DTPA-Rituximab in the popliteal node (2.6±0.6 %ID) with a popliteal extraction factor of 82.4±4.2% indicated good retention of the radiolabeled Rituximab by the B-cells present in the lymph node. Negligible activity was found further up in the lymphatic channel or in other organs. Conclusions: Rituximab was successfully labelled with 99m Tc using the carbonyl core and tested in Wistar rat footpad model for its suitability as a sentinel lymph node detection tracer. The results of this preliminary study indicate its potential as a SLN tracer for detecting sentinel lymph node in patients with breast cancer.
Development and characterization of Ga-68 labelled antimicrobial peptides as potential PET probes for the detection of human bacterial infections - A pre-clinical study
Shalini Chopra 1 , Baljinder Singh 1 , Anil K. Mishra 2 , Ashwani Koul 3 , Hans-Jόrgen Wester 4
1 Department of Nuclear Medicine and PET, Postgraduate Institute of Medical Education and Research, Chandigarh, 2 Division of Cyclotron and Radiopharmaceutical Sciences, Institute of Nuclear Medicine and Allied Sciences, DRDO, New Delhi, 3 Department of Biophysics, Panjab University, Chandigarh, India, 4 Department of Pharmaceutical Radiochemistry,Technical University of Munich, Walther-Meissner-Str. 3, 85748 Garching, Munich, Germany
Background and Aim: Antimicrobial peptides (AMPs) have a unique property to kill microorganisms and are seen as potential substitute for the conventional antibiotics. As a part of the innate host immunity and unlike antibiotics, bacteria do not develop any resistance against them. Therefore, radiolabelling of AMPs with positron emitters ( 68 Ga) may provide specific molecular probes for the accurate detection of active bacterial human infections. The aim of the present study was to synthesize and characterize DOTA-AMP conjugates, standardization of 68 Ga radiolabelling conditions and pre-clinical evaluation by using small animal PET imaging. Materials and Methods: The peptide fragments GF-17 and RAWVAWR-NH 2 (active against both gram positive and negative bacteria) were synthesised by solid phase peptide synthesis. DOTA coupling for GF-17 and RAWVAWR-NH 2 was done in solution phase and solid phase respectively. Purification and characterization were done by HPLC and mass spectroscopy. DOTA-peptide conjugates (20.0 µL; 1 mmol/mL) were radiolabelled with 68 Ga in 800.0 µL of sodium acetate:acetic acid buffer (pH 4) by heating at temperature of 95°C for approximately 25.0 min. The radiolabelled compounds were purified by using C8 SPE cartridge. Quality control tests were performed for 68 Ga-DOTA-GF-17 and 68 Ga-DOTA-RAWVAWR-NH 2 . PET imaging (Inveon, Siemens, Animal PET scanner) was performed in normal Balb/c mice following i.v. administration of 20.0-25.0 MBq of each of the 68Ga-labeled peptides. Results: The mass spectroscopy analysis demonstrated that the molecular masses of DOTA-GF-17, and DOTA-RAWVAWR-NH 2 were 2487.2 (calculated mass 2487.44) and 1328.9 (calculated mass 1328.71) respectively. The radiolabelling efficiencies for 68 Ga-DOTA-GF-17 and 68 Ga-DOTA-RAWVAWR-NH 2 were found to be 95.0% and 96.0 % respectively and remained stable for up to 3h. The plasma protein binding and lipophilicity for 68 Ga-DOTA-GF-17 were 80.98% and -3.12; and that for 68 Ga-DOTA-RAWVAWR-NH 2 were 40.98% and -0.81 respectively. Rf value for both the compounds was 0.1 ( Stationary phase: TLC SG, mobile phase: 0.1M sodium citrate). 68 Ga-DOTA-GF-17 PET dynamic images (90 min) showed initial uptake in heart, liver, kidneys and low grade uptake in bone marrow and muscles. There was significant clearance of tracer from the heart and liver. However, the clearance from the kidneys was minimal. 68 Ga- DOTA-RAWVAWR-NH 2 PET static image (90 min) demonstrated intense uptake of the tracer in kidneys with excretion into the urinary bladder, moderate grade uptake in the liver, salivary glands, blood pool and bone marrow and minimal uptake in the muscles. Conclusion: A successful radiolabelling of 68 Ga with GF-17 & RAWVAWR-NH 2 was achieved. The normal bio distribution pattern of 68 Ga labelled peptides in bone, muscles and fast clearance from liver may be useful for targeting of bacterial infections in these areas. However, the potential of these radiopharmaceuticals for infection imaging requires further pre-clinical validation before translation to clinical use.
Experience of non metallic silica based 68Ge/68Ga ITG generator: 68Ga labelled radiopharmaceuticals
Bhakti Shetye, Priya Monteiro, Mehjabeen Pathan, Ashish Zha, V. Rangarajan, N. Purandare, Sneha Shah, Archi Agrawal
Department of Nuclear Medicine and Molecular Imaging, Tata Memorial Hospital, Mumbai, India
Background and Aim: Continuous development of 68Ge/68Ga generator system open a new era in development of 68Ga labelled radiopharmaceuticals. Earlier generator system used metallic column made up of alumina, TiO2, SnO 2 and pyrogallolformaldehyde organic resin as an adsorbent. ITG developed new generator system which uses non-metallic silica based column and 0.05M HCL as eluate. Non-metallic column yields Ga (III) in pure ionic form which further improves final yield of labelled product. Hence, we have evaluated labelling efficiency of 68Ga labelled radiopharmaceuticals using ITG 68Ge/68Ga generator system. Materials and Methods: We assessed the labelling performance of two ITG 68Ge/68Ga generator systems of 30mci each. ITG provided self-shielded iQS fluidic module for labelling purpose. First generator was replaced after six month of installation. We performed 33 labelling procedure for 68Ga-DOTANOC and 10 for PSMA using first generator. After inception of second generator since July 2015, we labelled 68Ga -PSMA (n = 30) and 68Ga-DOTANOC (n = 13). 25 µgm of peptide (DOTANOC Acetate) and 900µl of 0.25M sodium acetate was used for labelling with 68Ga. For 68Ga-PSMA labelling 5 µgm of peptide (DKFZ-PSMA- 11) and 1ml 0f 0.25M sodium acetate buffer was used. Elution was done with 0.05M HCL. After heating for 10 min at 100 0 C labelled 68Ga-DOTANOC product was passed through C8 cartridge and 68Ga-PSMA through C18 cartridge. Labelled product was extracted with 50% ethanol as an eluent. Waste and product got collected in separate vials. pH of labelled product was measured. Radiochemical purity of 68Ga-DOTANOC was determined by ITLC method using 0.1M tri-sodium acetate as a solvent. Radiochemical stability was evaluated after 2-3 hrs. Results and Conclusion : We calculated labelling efficiency of 68Ga labelled product using both generators. Using first generator labelling efficiency of 68Ga-DOTANOC was 71% (n = 24, SDEV=0.065, pH=5.5).Low yield was reported nine times (40-55%). Low yield of 68Ga-PSMA was 45-60% (n = 3). Labelling efficiency of 68Ga-PSMA was79 % (n = 7, SDEV=0.072, pH=5.5). Radiochemical purity was >93%. RCP was >90% after 3 hrs.
Synthesis Evaluation and Comparison of 99m Tc labelled choline derivativesas potential SPECT agents for targeting prostate cancer
Ambika Parmar Jaswal 1 , Surbhi Prakash 1 , Viren K Meena 1 , Ankita Pandey 1 , Harleen Khurana 1 , Baljinder Singh 2 , Sarika Sharma 2 , Anil K Mishra 1 * and Puja P. Hazari 1 *
1 Division of Cyclotron and Radiopharmaceutical Sciences, Institute of Nuclear Medicine and Allied Sciences, Brig S.K. Mujumdar Road, Delhi, 2 Department of Nuclear Medicine PGIMER Chandigarh, India
Background and Aim: Abnormal choline metabolism is known to be associated with oncogenesis and tumour progression. The enhanced choline uptake and phosphorylation in tumour cells has motivated the development of radiolabelled choline derivatives as diagnostic markers for imaging cell membrane proliferation. The goal of this work is preclinical evaluation and comparison of choline conjugated to polyamino polycarboxylate chelating agent (DTPA-bis-choline) and dithiocarbamate (Choline-DTC), both radiocomplexed to [ 99m Tc] for potential tumour imaging applications. Materials and Methods: The synthesis of DTPA-bis-choline and Choline-DTC featured quaternization of dimethylaminoethanol with bromoethylamine which act as linker followed by conjugation of highly active primary amine to DTPA anhydride and Carbon disulphide. Both the derivatives were evaluated in-vitro for cell binding, cytotoxicity, tumour kinetics in PC-3 cell line, whereas in vivo evaluation in terms of biodistribution, imaging and toxicity were performed in Balb/c mice. Sterile kit formulation of DTPA-bis-choline and choline -DTC were prepared for clinical purpose. Results: The pharmacokinetic studies of both [ 99m Tc]-labelled DTPA-bis-choline and [ 99m Tc]-labelled Choline-DTC in mice shows high tumour to background ratio after few minutes of intravenous administration. Stability studies showed that the conjugates were stable even after 24 h in serum sample. Preclinical findings showed a good visualization of lesions in EAT Balb/C models and PC-3 athymic mice models with a high target to non-target ratio. Conclusion : Preliminary preclinical data suggests [ 99m Tc]-Choline-DTC as a better prostate visualizing agent in comparison to [ 99m Tc]-DTPA-bis-choline owing to its lypophilicity and hepatobilliary route of excretion.
Targeting intravascular thrombosis using 68 Ga-DO3A-EAm-anti-α v ß 3 immunoconjugate as a PET imaging agent
Ankita Pandey 1 , Puja Panwar Hazari 1 and Anil K Mishra 1
1 Division of Cyclotron and Radiopharmaceutical Sciences, Institute of Nuclear Medicine and Allied Sciences, DRDO, New Delhi - 110 052, India
Background and Aim: Intravascular thrombosis is the major cause of morbidity and mortality worldwide. Previous studies regarding diagnosis of thrombus using radiolabelled antibodies targeting fibrin, activated platelets, plasminogen, plasmin, factor XIII have shown promising results. These new tracers are anticipated to be able to aid the presently used modalities for detection of intravascular thrombosis. Integrin α v ß 3 at thrombogenic sites have been described as the attractive targets for diagnosis and therapy of thrombotic disorders. Therefore, the goal of the present study was to evaluate the feasibility of radiolabelled anti-α v ß 3 -(DO3A-EA) immunoconjugate in positron emission tomography (PET) imaging of α v ß 3 overexpression in animal models of thrombosis. Materials and Methods: A thermodynamically stable chelate, 1,4,7-tris(carboxymethyl)-10-(2-bromoethyl)-1,4,7,10-tetraazacyclododecane (DO3A-EB) and anti-α v ß 3 conjugate was developed as thrombus specific imaging agent. DO3A-EB conjugation with anti-α v ß 3 was performed and subjected to purification on size exclusion chromatography. The DO3A-EA conjugated antibodies were labelled with 68 Ga with a radiolabelling efficiency of >80 %. Specific activity observed was 20-30 mCi/mg of protein. 68 Ga-DO3A-EAm-anti-α v ß 3 conjugate was injected intravenously and analysed in the mouse model of pulmonary thromboembolism and flow restriction model of deep vein thrombosis in rats, to assess its thrombus binding capability and specificity using in vivo PET analysis. Results: Pharmacokinetic and biodistribution studies confirmed long circulation times (t 1/2 (fast)=48 min and t 1/2 (slow)=11 h 5 min) and efficient accumulation in thrombus. Biodistribution studies in the mouse model of pulmonary thromboembolism and flow restriction deep vein thrombosis in rats revealed significant localization of 68 Ga-labeled antibody conjugate in thrombus and minimal non-target accumulation. Conclusion: Anti-α v ß 3 -(DO3A-EA) immunoconjugate is a promising radiotracer for immunoscintigraphy since good thrombus-to-normal organ contrast could be observed. These properties can be exploited for immunospecifc imaging agent in nuclear medicine for arterial or deep vein thrombotic complications. Therefore the present study may provide a powerful diagnostic tool for the assessment of acute or chronic thrombosis in patients in the future.
Development of Indigenous, Low Cost SPE-Purification Method for 2[F-18] FDG Production
Nayak Shrinibas, Lakshminarayan N, MGR Rajan
Radiation Medicine Centre, BARC, Parel, Mumbai - 400012, India
Background and Aim: 2-[F-18]FDG is the workhorse of PET-imaging studies in Nuclear Medicine(NM) viz, in Cardiology, Neurology and Oncology. FDG is produced at the Medical Cyclotron Facility at RMC via S N 2 reaction between mannose triflate and [F18]TBAF in acetonitrile followed by acid (or alkali) hydrolysis and solid phase purification using a Chromabond IV (Macherey Nagel), which contains four different layers of cation, anion exchange columns, neutral alumina and HRP columns. Due to the high cost and import of the CHROMABOND IV column, we have developed a solid phase extraction method using readily and locally available columns. Materials and Methods : Cation exchange column (MN-731861), Neutral alumina (Macherey Nagel-731844 or Water-WAT020510), C18 column(Water-WAT020515) are readily available locally, and were used after conditioning each with 10ml of absolute ethanol followed by 20ml of water. For anion exchange column, Dowex resin 1X8 chloride form, 100-200 mesh size (Sigma-Aldrich, Ref No-217425) was used. 800-850mg of Dowex resin was used each time after passing 20ml of saturated bicarbonate solution followed by 40 ml water. The combination of different columns was used in sequence from top to bottom as cation, anion, alumina and C18. Results and Discussion: The sequence of solid phase columns used for purification was preliminarily based on the Chromabond IV column used in the purification step of FDG production. FDG is basically trapped in neutral alumina during loading of the reaction mixture. Since the reaction mixture is highly acidic (1M HCl/1mL), it is essential to neutralize the acid before it comes in contact with the neutral alumina. Otherwise, alumina will be solubilized by acid, and will come into the product in the purification process. Further, when the pH of the product is brought down to the required range (4.5 - 8.0) fine aluminium phosphate precipitate was formed. The weight of Dowex resin chosen in bicarbonate form (based on milli-equivalent) was optimized to neutralize the hydrochloric acid used in the hydrolysis step and to trap unreacted [F-18]-fluoride from the reaction mixture. Several batches of FDG (activities of the range 25GBq to 120GBq) have been produced and tested for its yield, reliability, consistency, chemical and radio-chemical purity, presence of Aluminium ion, pH, Sterility and BET, and found comparable and satisfactory. Yield of FDG was between 55-65%, radiochemical purity was >98%, Aluminium ion impurity(Al 3+) was <5μg/mL and pH was between 5.5-6. All batches passed sterility and endotoxin tests. The method has been adopted for regular production and over 120 batches of 2[F-18]FDG have been produced. Conclusion: Indigenous and economic solid phase extraction method for the purification of [F-18]FDG was successfully developed. The method has been logically developed and tested exhaustively and the results are found to be satisfactory, reliable and consistent for all the QC tests for product compliance. The process is being used successfully for the regular production of FDG.
Performance Evaluation of Prototype Thyroid Uptake Probe made by BARC
Awasare SU, Biju K, Chaturvedi P*, Panchal C # , Moghe SH, Baghel NS & Rajan MGR
Radiation Medicine Centre, BARC, TMC Annex, Parel, Mumbai - 400 012, *Manipal Institute of Technology, Manipal, Kanrnataka, # Electronics Division, BARC, Trombay, Mumbai - 400 085, India
Background: The thyroid uptake probe is an integral part of a nuclear medicine department that investigates thyroid disorders. It is used to estimate the radioiodine uptake in the neck following the administration of a small amount of radioactive iodine-131. The probe comprises of - a flat field collimator, NaI(Tl) crystal, photomultiplier tube, preamplifier, amplifier and a counter/scalar unit. Performance of the thyroid uptake probe is evaluated by carrying out - counting statistics and χ2 -test, detector shielding test, sensitivity test, stability test, linearity of response, energy resolution etc. These tests were applied to the prototype thyroid probe made at BARC, to check its suitability for routine use. Aims: To evaluate the BARC thyroid probe by carrying out the various performance tests prior to its use for routine uptake studies. Materials and Methods: The Electronics Division, BARC, developed a thyroid uptake probe with interface electronics and required software to use it with a standard PC. This stand-alone machine was evaluated for its performance at RMC. Its counting statistics and χ2 -test of observed and expected counts was carried out with a suitably placed 25uCi 131 I capsule,. Detector shielding test was performed by placing a 131 I source in various positions viz., front, sides, back, close left, close right etc. Sensitivity of the probe was calculated using known 131 I and 137 Cs sources. Linearity of radioactivity response was compared using ~0.5mCi/100µl of 99m Tc and taking counts at different time intervals. Energy resolution was by plotting energy spectrums using 57 Co, 137 Cs, 131 I and 99m Tc sources. Linearity of energy response was also performed. Iso-response curve was drawn using 57 Co by keeping the source at different locations in front of the uptake probe. An old thyroid probe (still in use at RMC) manufactured by Nuclear Chicago, USA, about 30 years ago and, which is an industry standard was also evaluated for comparison. Results: The thyroid uptake probe made in BARC was found to have acceptable performance parameters. Moreover, the fabricated probe showed better sensitivity and percent energy resolution than the old uptake probe. Conclusions: The BARC made thyroid uptake probe had acceptable performance parameters and is suitable for patient use. The computer interface and software enabled user-friendliness and patient through-put.
Use of telemedicine for facilitation of follow-up of patients of hyperthyroidism after definitive therapy with radioiodine in a primarily hilly state
Vandana K. Dhingra, Nisha Bhatia
Department of Nuclear Medicine, Cancer Research Institute, SRHU, Dehradun
Background and Aim: The need for observation for the first few weeks post after radioiodine therapy is important especially in patients with borderline and severe thyrotoxicosis. Telemedicine is the use of telecommunication and information technologies in order to provide clinical health care at a distance. In a primarily hilly state of Uttrakhand most patients come from long and difficult (hilly) distances, this can impact compliance of follow-up. Materials and Methods : We developed a pilot protocol for using telemedicine for management of patients planned for radioiodine therapy for hyperthyroidism. This involved a two-step approach involving telemedicine prior to therapy and for post therapy follow-up. Step One: Planning and active calling. On the first visit after referral for radioiodine therapy telephone and e-mail details of patients were noted. Counseling and details of radioiodine therapy were also explained and patients were asked to come on call for the radioiodine therapy. Patients who were on higher side dose of antithyroid drugs >30mg of carbimazole per day underwent thyroid biochemistry on the day of therapy for exact status of thyroid function. Step Two: Post radioiodine therapy active tele-follow-up. Telephonic/e-mail information was taken regarding the well-being of all patients twice during the first 4-6 weeks and they were also informed about the results of their biochemistry tests on therapy day. Patients visited physically at 12 weeks. Results: We included 46 consecutive patients with diagnosed hyperthyroidism referred for therapy for this protocol. This included 39 females, 5 males and 2 patients less than 18 years. Age range was 13 to 70 years. All patients received radioactive iodine on the planned day. They came from a distance ranging from 15-200 km from our Institute (mostly hilly terrain). Of these 8 patients which included one paediatric patient had severe thyrotoxicosis controlled on very high dose of antithyroid medications. This method reduced 92 patient visits (two visits per patient) and ensured well-being post radioiodine administration. Patient compliance and satisfaction was better. Radioiodine therapy was given in a planned way i.e. required dose was ordered and utilized. Conclusion: Organized use of telemedicine for planning therapy and post therapy follow-up for patients treated with radioiodine for hyperthyroidism resulted in better compliance of follow-up and reduced the number of outpatient visits. This was especially helpful for patients coming from remote areas. It also resulted in better patient satisfaction. This method also helped us to utilize radioisotope effectively.
Clinical features, treatment outcomes and prognosis of differentiated thyroid carcinoma (DTC) in pediatric population - Our institutional experience
Sibu Jacob, Shelley S., Indirani M., Jaykanth, Avani, Shilpa, Thangalakshmi
Department of Nuclear Medicine and PET/CT, Apollo Hospitals, Chennai, Tamil Nadu, India
Background and Aim: A change in concepts regarding the management of DTC in pediatric population is necessary since it differs from adults in terms of incidence, clinical presentation, course of disease, approach to treatment, long term prognosis etc. Mere extrapolation of the common therapeutic practices done in adults, to the pediatric population doesn't seem to work well. The aim of this study is thus to analyse demography, clinical features and clinical outcomes of thyroid carcinoma in pediatric population. Materials and Methods: Retrospective observational study done during the year 2009 - 2014, a total of 20 patients of age </= 18 years were included, of which 16 were females and 4 males. The mean age of presentation was 16.6 years. 6 patients underwent total thyroidectomy (T.T.) and 14 patients had T.T. with nodal dissection considering the preoperative ultrasound findings and risk stratification of the disease. The histological, clinical, metastatic status and prognosis was then evaluated. Results: Palpable neck mass was the most common reason for consultation with papillary carcinoma of thyroid being the commonest histological finding (90% vs follicular carcinoma - 10%). Extracapsular and vascular invasion was seen in 70% of the patients with 30% having localized disease. Metastatic nodes were found in 65% of patients while 10% had lung metastases. The mean size of the primary tumor was 3.3 cm (range 1.2-8.0 cm). All patients underwent I-131 radiation ablation therapy. Follow up was done in 13 patients of whom 12 patients showed response to therapy and 1 showed progression. Conclusions: Our study shows that compared to adults, pediatric thyroid carcinoma has aggressive features at initial diagnosis and comprehensive surgical treatment with near total or total thyroidectomy should be considered, with nodal dissection where conventional imaging showed nodal metastases or patients with high risk tumour characteristics (viz multifocality, bilaterality, extracapsular extension). I-131 radiation ablation was considered as an adjuvant treatment; to prolong the disease free survival and to increase the diagnostic accuracy of follow up serum thyroglobulin and I-131 whole body scan (I-131WBS) wherever clinically warranted. Follow up with neck ultrasound and serum thyroglobulin is sufficient and routine I-131WBS is not recommended unless there is persistent/recurrent disease.
To determine the reliability of stimulated serum thyroglobulin levels over unstimulated serum thyroglobulin in the management of post-thyroidectomy patients with papillary thyroid carcinoma
Saumya Sara Sunny, Julie Hephzibah, David Mathew, Nylla Shanthly, Regi Oommen
Department of Nuclear Medicine, Christian Medical College, Vellore, India
Background and Aim : Serum thyroglobulin and whole body radioiodine scintigraphy (TWBS) are routinely used in the follow up of patients with papillary thyroid carcinoma (PTC) after total thyroidectomy. As patients are required to stop thyroxine for a period of one month prior to their visit, symptoms of hypothyroidism are frequent. Recently there has been a practice of following up these patients with unstimulated serum thyroglobulin (uSTg) only. Materials and Methods : Retrospective analysis of data of post- thyroidectomy patients with PTC (n= 295) between December 2014 and September 2015 was done. Among them, all patients with both uSTg and sSTg levels measured within a gap of about 6 months were studied and risk stratification done as per ATA guidelines 2009. In our institution, intervention is based on a cut-off value of STg > 10 ng/ml. Hence for this study, the same cut-off value was used for data analysis. Results : Out of 295 patients, 36 patients had fulfilled the above criteria. Of the 36 patients studied, low, intermediate and high risk groups comprised of 12 patients each. sSTg>10 ng/ml with uSTg < 10ng/ml in the same patient was noted in: 25% (3/12) of the low risk, 41.6% (5/12) of the intermediate risk and 8% (1/12) of the high risk group. STg levels were corroborated with tumour burden as determined by additional clinical, USG neck and TWBS findings. These patients would have been overlooked and falsely assured of a disease free status, if only uSTg was considered.