|Year : 2016 | Volume
| Issue : 5 | Page : 4-28
|Date of Web Publication||7-Nov-2016|
Source of Support: None, Conflict of Interest: None
|How to cite this article:|
. Oral Presentation
. Indian J Nucl Med 2016;31, Suppl S1:4-28
| Instrumentation and Medical Physics|| |
Design and development of thyroid uptake system
G. Venkateswara Rao, Sameer Bhatt, K. N. Karn, P. I. Hadgali, S. P. Srivastava, C. G. Panchal 1 , Sushama Awasare 2
Centre for Design and Manufacture, Bhabha Atomic Research Centre, 1 Electronics Division, Bhabha Atomic Research Centre, 2 Radiation Medicine Centre, Bhabha Atomic Research Centre, Mumbai, Maharashtra, India
Objective: Thyroid scan uses radioactive tracers and a special camera (thyroid probe) to acquire the information about the size, shape, position, and function of the thyroid gland that is often unattainable using other imaging procedures. It is required to design and develop a complete, mobile, self-contained medical spectrometer that makes probe positioning for uptake studies simple and comfortable with accurate, repeatable patient positioning, and inbuilt redundant safety features. Description: The thyroid uptake system is an advanced multipurpose spectrum analysis instrument designed for diverse nuclear medicine applications. Uptake studies and other user-defined tasks are accomplished with speed and precision using this manually controlled instrument along with application software. Engineered for mobility, durability, and operational efficiency, the system handles clinical tests, safety compliance tasks, and system administration procedures quickly and accurately. The self-contained system is configured on a compact mobile platform with locking castors. A f5 cm NaI (Tl) detector assembly with collimator shield articulates on a multi-axes and height-adjustable counterbalanced arm. The 45 cm of vertical travel allows the probe to be positioned from 94 to 137 cm in the horizontal position from the floor to accommodate seated or supine patients. The probe swings −90°-15° on the horizontal plane and extends outward up to 35 cm horizontally from the support column. This design makes positioning for uptake studies simple and comfortable for both patient and technologist. The distance measurement scale assures accurate, repeatable patient positioning and uptake measurements. Conclusion: The thyroid uptake system has been successfully designed, developed, and manufactured fulfilling all the operational and safety requirements.
Comparison of volume estimation of low-dose computed tomography and diagnostic computed tomography of a liver phantom
Shivani Choudhary 1,2 , Sanajy Gambhir 1 , Subhash Chand Kheruka 1 , Narvesh Kumar 1 , Nilesh Shankar 1,2 , Ramesh Chandra 2
1 Department of Nuclear Medicine, SGPGIMS, 2 Department of Applied Physics, BBA University, Lucknow, Uttar Pradesh, India
Objective: Comparison of volume estimation of low-dose computed tomography (CT) and diagnostic CT of a liver phantom and to measure radiation dose during low and diagnostic CT. Methods: Ten values were taken using anthropomorphic single-photon emission computed tomography phantom where the liver phantom was filled with known amount of glycerin (used as a contrast) with 4 mci of 99m Tc-pertechnetate. The examinations were undertaken on a GE 64-slice diagnostic CT machine with Xeleris software. A standard adult abdominal imaging protocol was used; parameters applied on diagnostic CT were current 271 mA, voltage 140 kv, and matrix size 512 × 512. Low-dose CT was performed on GE Infinia Hawkeye low-dose 4-slice CT scanner; the parameters applied on low-dose CT were current 2.5 mA, voltage 140 kV, and matrix size 512 × 512. The images of CT were processed in Xeleris workstation, GE Healthcare. Functional volume was calculated using volume estimation program in Xeleris software. Results: The average radiation dose with low-dose CT was 15.46 mGy and average high-dose CT radiation dose was 58.48 mGy. Radiation dose was drastically reduced with copper filter which was 7.72 mGy only. The average volume with low-dose CT was 1869 cm 3 , with copper filter it was 1852 cm 3 , and average volume with diagnostic CT was 1980 cm 3 . Actual known volume was 1870 cm 3 . Hence, no statistically significant difference in volume estimation was noted in low-dose or diagnostic CT. Conclusion: In our study, we concluded that there was no significant difference in volume estimated with low-dose CT study and diagnostic CT study, but there was significant reduction in radiation dose delivered during each scan. Hence, we recommended that to implement ALARA practice and diagnostic reference levels, we should use low-dose CT study in place of diagnostic CT study to estimate future remnant liver volume.
Estimation of radiation dose to caregiver of patients treated with high-dose iodine-131 using thermoluminescent dosimetry
Nilesh Shankar 1,2 , Subhash Chand Kheruka 1 , Narvesh Kumar 1 , Deepanksha Datta 1 , Shivani Choudhary 1,2 , Sanajy Gambhir 1 , Ramesh Chandra 2
1 Department of Nuclear Medicine, SGPGIMS, 2 Department of Applied Physics, BBA University, Lucknow, Uttar Pradesh, India
Objective: The aim of this study was to determine whether high-dose radioactive iodine 131 I treatment of patients with differentiated thyroid carcinoma as an outpatient is a pragmatically safe approach, particularly for the safety of caregivers, following the release of the high-dose radioactive iodine I-131-treated patients. Methods: The administered activity ranged from 50 mCi to 200 mCi. One or two designated caregivers received specific radiation safety training before treatment. One caregiver was allowed to stay adjacent to the room of the patient to provide general patient care and support. Twenty-two patients (8 male and 14 female), with differentiated thyroid carcinoma, referred to the Department of Nuclear Medicine at SGPGIMS Lucknow, Uttar Pradesh, were treated with high-dose radioiodine I-131. Following the discharge, the caregivers were provided with a thermoluminescent dosimetry (TLD) crystal in the form of a locket to be worn in the neck. Cumulative radiation dose over a period of 7 days postadministration of I-131 was measured. The TLD crystal was analyzed in TLD reader. Results: Variable results of cumulative exposure to the caregivers were obtained with different doses of high dose of oral I-131. The maximum dose received by the caregivers was 24.25 mGy (24250 µSv), and the minimum dose received was 9.73 mGy (97,330 µSv). The common supporting and caring activities done by the caregivers in the 1 st week of the oral administration of radioiodine includes travelling together in the common vehicle, eating and sleeping in the next room, and providing food and medications. Most of the patients recruited in the present study had Karnofsky performance score >60, that is, they did not need any assistance in their daily activities. Conclusions: The radiation doses to caregivers from comforting and caring of hospitalized inpatients treated with I-131 for thyroid cancer increased with increasing administered dose to the patient but showed variable results.
Imaging of bremsstrahlung radiation for 90 Y citrate radiation synovectomy in hemophiliac joint arthropathy
Mangala Ghorpade, Suruchi Shetye, Shwetal Pawar, Ashish Kamra
Seth G. S. Medical College and K. E. M. Hospital, Parel, Mumbai, Maharashtra, India
Aim: Arthropathy is a frequent complication of repeated intra-articular bleeding in patients with hemophilia, causing pain, deformity, and disability. The purpose of study was to image the bremsstrahlung radiation after intra-articular injection of Y-90 citrate in hemophilic joint arthropathy comparing planar and single-photon emission computed tomography/computed tomography (SPECT/CT) images. Materials and Methods: Twenty joints (17 knees, 2 elbows, and 1 ankle) were selected for radiation synovectomy with repeated (>3) intra-articular bleeds over 6 months causing disability and restriction of movement. They were injected intra-articularly with 90 Y-citrate (185 MBq in knee joint and 111 MBq in elbow and ankle joints). The intra-articular localization of 90 Y-citrate was confirmed using bremsstrahlung radiation: planar and SPECT-CT images. The planar images were acquired immediately after intra-articular injection in anterior and posterior projections using medium-energy general purpose collimator and setting 140 KeV as peak with −64.29% and +56% window. SPECT/CT imaging was performed using a 128 × 128 image matrix for 32 projections over 180° for each camera head (a total of 64 projections over 360°) for 20 s per projection using the auto contour rotation mode. The reconstruction of images was done using ordered subset expectation maximization. Results: The images acquired for intra-articular localization of Y-90 citrate was best assess using SPECT/CT images than planar. The pockets of joint cavity were well visualized in all the joints. Sixteen patients showed spread of radiopharmaceutical in entire joint cavity and four patients showed localization of radiopharmaceutical in one chamber of joint cavity. These patients were in advanced stage of arthritis. All the patients showed improvement in the joint function and reduction in number of bleeding episodes. Conclusion: SPECT/CT images provide better information of localization of radiopharmaceutical in the joint cavity. The imaging protocol used provided us with excellent quality images.
Evaluation of the effect of varying target to background ratio using NEMA NU-2-2001 body phantom for image quality
Ankit Watts, Rohit Rana, Baljinder Singh, Ashwani Sood, B. R. Mittal
Department of Nuclear Medicine and Positron Emission Tomography, A/10 GF, Nehru Hospital, PGIMER, Chandigarh, India
Aim: The aim of the study was to investigate the effect of time of flight (TOF) on image quality by varying target:background ratio (TBR) using NEMA NU2 IQ phantom and to optimize an ideal scan time per bed position that may be replicated in clinical settings. Materials and Methods: In this study, acquisitions were done on prototype positron emission tomography scanner (GE Discovery 710). NEMA-IQ NU-2007 body phantom was filled in way to obtain TBR of 4:1, 6:1, 8:1, and 10:1. Data were acquired in two replications using both TOF and non-TOF modes for all the above-mentioned TBR. The list mode data were re-binned to 1, 1.5, 2, and 2.5 min for quantitative analysis. Data Analysis: Contrast recovery coefficient and background variability were computed using NEMA analysis software. Region of interests (ROIs) were drawn over the hot and cold spheres on the axial slice that showed all the spheres with maximum intensity. Background (60 ROIs) mean and standard deviation values and sphere ROIs values were computed to obtain signal-to-noise ratio (SNR), contrast and noise values using appropriate formulae. Results: Incorporation of TOF resulted in reduction of image noise; hence, the smallest sphere (10 mm) showed better contrast recovery coefficient, SNR, contrast values for TOF data as compared to non-TOF in all TBRs. Shorter scan time per bed position (1and 1.5 min) dissipated better contrast and SNR values in TOF as compared to non-TOF images in all TBR. SNR values of TOF were found to be statistically different from non-TOF data at TBR of 4:1 (P = 0.048) whereas nonsignificant at 6:1 (P = 0.1), 8:1 (P = 0.5), and 10:1 (P = 0.076). Similarly, contrast values were found to be significantly different at TBR 4:1 (P = 0.012) and 6:1 (P = 0.005) and nonsignificant at 8:1 (P = 0.7) and 10:1 (P = 0.71). Conclusion : Images with TOF give better image quality than non-TOF substantially at lower TBR. The detection of small lesion was better in TOF compared to non-TOF images at shorter acquisition time per bed position. Hence, the scan time per bed position may be done with 1.5 min without compromising the image quality.
| Radiochemistry and Radiopharmacy|| |
Synthesis and comparative evaluation of 68 Ga-HBED-CC-c (RGDfK) and 68 Ga-HBED-CC-c (KCNGRC)
Drishty Satpati, Yugandhara Pamale, Haladhar Dev Sarma, Sharmila Banerjee
Radiopharmaceuticals Chemistry Section, Bhabha Atomic Research Center, Radiation Biology and Health Sciences Division, Bhabha Atomic Research Center, Trombay, Mumbai, Maharashtra, India
Objective: Asparagine-glycine-arginine (NGR) sequence containing peptides binds efficiently to aminopeptidase N receptors (CD13) upregulated in angiogenic blood vessels and various human solid tumors, including melanoma, prostate, lung, and ovarian cancer. In this study, the acyclic chelator, HBED-CC, has been conjugated to the peptides c(KCNGRC) and c(RGDfK) and radiolabeled with 68Ga for evaluation as tumor-targeting molecular probes. Materials and Methods: The peptide-conjugate HBED-CC-c(KCNGRC) (1) was synthesized using standard Fmoc solid-phase peptide chemistry. Subsequent to on-resin cyclization with Tl (III)-trifluoroacetate, the peptide was cleaved and purified using semipreparative HPLC. HBED-CC-c(RGDfK) (2) was synthesized in solution phase using the commercially procured cRGDfK peptide. For radiolabeling, 68 Ga (37 MBq) eluted from 68Ge/68Ga generator (Eckert and Ziegler) was added to HBED-CC-c(KCNGRC)/c(RGDfK) (20 µg) dissolved in sodium acetate buffer (200 µL, 1.5 M, pH 4) and incubated (80°C, 5 min). In vivo evaluation of the two radiotracers was carried out in C57BL6 mice bearing melanoma tumor. Results: HBED-CC-c(KCNGRC)/c(RGDfK) could be synthesized in >99% purity. The radiochemical yield of 68 Ga-1 and 68 Ga-2 was >98% as determined by HPLC and paper chromatography. 68 Ga-1 was slightly more hydrophilic than 68 Ga-2 (logP = −2.4 ± 0.1 and −2.2 ± 0.1, respectively). Higher retention in blood, kidneys, and intestine was observed for 68 Ga-2 (2.0 ± 0.05, 7.0 ± 0.1, and 3.5 ± 0.6% ID/g, respectively) in comparison to 68 Ga-1 (1.6 ± 0.07, 5.7 ± 0.7, and 1.5 ± 0.07% ID/g). Tumor uptake of the two radiotracers was nearly similar ( 68 Ga-1: 1.5 ± 0.07% and 68 Ga-2: 1.2 ± 0.1% ID/g). Blocking studies with excess cold peptide reduced the tumor uptake by 50%-60% for the two radiotracers. Conclusion: The two radiotracers have the potential for further detailed evaluation as molecular probes for angiogenesis imaging.
Comparison of the cytotoxic effects of 131 I-meta-iodobenzylguanidine on the human neuroblastoma cell lines SK-N-SH and IMR-32
Shubhangi Mirapurkar, Sheela Muralidharan, Navin Sakhare, Anupam Mathur, N. C. Joseph, S. S. Sachdev
Radiopharmaceuticals Program, Board of Radiation and Isotope Technology, Navi Mumbai, Maharashtra, India
Objective: 131 I-meta-iodobenzylguanidine ( 131 I-mIBG) is used for diagnosis as well as therapy of neuroblastomas. 131 I-mIBG enters in these tumors by active uptake Type 1 mechanism. Once internalized, its diagnostic or therapeutic efficiency depends on its cellular retention. The present study evaluates the basic mechanisms of mIBG/neuroblastoma interaction such as uptake, storage, and efflux, which contribute to its behavior as diagnostic/therapeutic radiopharmaceutical. This was carried out by studying the cell cytotoxic studies of 131 I-mIBG on two human neuroblastoma cell lines SK-N-SH and IMR-32 with different specific activities and concentrations of the radioactive tracer. Methods: Both cell lines (1 × 10 6 cells/well) were incubated with different activity concentrations (10-200 µCi) and different specific activities (5-100 µCi/µg) of 131 I-mIBG for 1 h. On completion of the incubation period, the cells were washed so that no trace of activity was present in the surrounding medium. The cells were further incubated for 72 h and the medium surrounding the cells was checked periodically for activity so that uptake and storage could be studied. Finally, after the incubation period, cytotoxic effect of 131 I-mIBG was studied by checking the viability of the cells. Results: Using different activity 131 I-mIBG concentrations (10-200 µCi), SK-N-SH cells died in a dose-dependent manner while IMR-32 cells remained healthy. This may be due to known long periods of retention of mIBG in SK-N-SH cell vesicles, which is not expressed in IMR-32. Furthermore, the cytotoxic effect in SK-N-SH was more pronounced with higher specific activity (80-100 µCi/µg) than low specific activity (5-10 µCi/µg) of 131 I-mIBG. Conclusion: The present in vitro cell uptake studies investigated the differential nature of 131 I-mIBG in neuroblastoma patients and confirmed that tumor uptake/efficacy of the agent in vivo is determined by the nature of cell type expressed in a particular neuroblastoma.
Preliminary evaluation of synthesis and quality control results for 68 Ga-labeled exendin using an automated module
Rajeev Kumar, Nishikant A. Damle, Madhavi Tripathi, Arun Raj, Chandrasekhar Bal
Department of Nuclear medicine, Positron Emission Tomography and Cyclotron Facility, AIIMS, New Delhi, India
Objective: To share our experience regarding the synthesis and quality control of generator-based 68 Ga-labeled exendin using an automated module. Methods: A 50 mCi 68 Ge/ 68 Ga generator (ITG, Germany) was eluted with 0.05 M HCl. Eluate in the form of gallium chloride was passed through a cation exchange. It removes the impurities and preconcentrates the solution. 68 GaCl 3 was adsorbed onto the cartridge and rest passed into waste. N2 solution (mixture of acetone, metal-free water, and concentrated HCl) was used to release concentrated and purified 68 Ga from the strata X-C cartridge, which then reached the reaction vial. This contained the precursor, i.e., exendin dissolved in metal-free water. The reaction vessel was kept at 80°C-85°C temperature for 18 min. It was then cooled and diluted by adding 3 ml of metal-free water. The product was transferred to the tC18 cartridge for purification. From this cartridge, the product was transferred into product vial with the help of pure ethanol. The product was passed through 0.22 µm Millipore filter and diluted by adding 25 ml normal saline in the product vial. All the synthesis steps were carried out in an automated module (Modular Lab, Eckert and Ziegler, Germany). Radiation levels were monitored outside the hot cell using portable radiation survey meter. The total synthesis time was approximately 36 min. Quality control testing (clarity, pH, and radiochemical purity) was performed using visual, pH paper, and thin layer chromatography scanner, respectively. Results: The maximum yield of 68 Ga-exendin was 19 mCi. The labeled preparation was clear with mean pH around 6.0. 68 Ga-exendin conjugate was prepared with very high radiochemical purity (99%). The product was stable up to 4 h. Outside the hot cell, radiation level was near to background level during the entire process. Conclusion: We formulated generator-based positron emission tomography radiotracer 68 Ga-exendin with high radiochemical purity and good stability using automated module.
Gastric ulcer scintigraphy using in-house labeled Tc-99m-sucralfate
Priya Bhusari 1,2 , Jaya Shukla 1,2 , Pallavi Sharma 1,2 , Rakesh Kochhar 1,2 , Anish Bhattacharya 1,2 , B. R. Mittal 1,2
Departments of 1 Nuclear Medicine and PET and 2 Gastroenterology, PGIMER, Chandigarh, India
Objective: Sucralfate is used for treatment of peptic ulcers due to its chemical complexation with the protein molecule exposed on ulcerative surfaces. This property of binding of sucralfate to the peptic ulcers has been exploited for imaging gastric as well as esophageal ulcers using in-house prepared Tc-99m-labeled sucralfate. Methods: Powdered sucralfate was used for radiolabeling with Tc-99m. Radiolabeling with Tc-99m was done using direct method with stannous reduction method. For optimization, varying amounts of sucralfate (10-50 mg) were used. The stannous concentration was varied between 0.3 and 0.8 mg. Other parameters for optimization included pH (1-7), volume of reaction mixture (1-4 mL), incubation time (10-30 min), and administration volumes (5-15 mL). Postradiolabeling, uncomplexed Tc-99m was separated from the Tc-99m-sucralfate suspension using centrifugation for 5 min at 2000 rpm. Quality control of Tc-99m-sucralfate was performed by radio-instant thin-layer chromatography. The pH of the diluted Tc-99m-sucralfate suspension was adjusted to 7 and administered to patient orally for gastric/esophageal ulcer scintigraphy, which was performed at different time intervals postadministration. Results: Sucralfate could be radiolabeled in-house in radiopharmacy laboratory using Tc-99m. Maximum radiolabeling could be achieved using 30 mg sucralfate in the presence of 0.35 mg stannous chloride at pH 3.5 by incubating the mixture for 15 min and restricting the maximum volume of reaction to 2 mL. The radiolabeling yield varied between 68% and 90%. Tc-99m-sucralfate was found stable up to 6 h postradiolabeling. Scintigraphy results demonstrated good in vivo stability in terms of binding of the Tc-99m-sucralfate complex to the ulcerative lesions. This allowed imaging up to 6 h at various intervals postadministration. Conclusion: Tc-99m-sucralfate can be prepared in-house and used as a potential radiopharmaceutical for scintigraphy of gastric and esophageal ulcers.
Synthesis and evaluation of arylpiperazinyl-alkyl benzoxazolone/benzothiazolone as a positron emission tomography radiotracer for 5HT7
Anjani K. Tiwari, Neelam Kumari, Anupama Datta, Anil K. Mishra
Division of Cyclotron and Radiopharmaceutical Sciences, Institute of Nuclear Medicine and Allied Sciences, New Delhi, India
Objective: The neurotransmitter serotonin (5-HT) is of particular interest because of its involvement in several neurological and psychiatric diseases. The most recent addition to the 5-HT receptor subtype is 5-HT7. It mediates key functions such as mood, sleep, memory, and cognition. Positron emission tomography (PET) provides an opportunity for in vivo observation in both animal models and humans, but no radioligands have been reached at clinical level to study 5-HT7 receptor in human. Methods: Here, we present the radiosynthesis and biological evaluation of arylpiperazinyl-alkyl benzoxazolone/benzothiazolone as a possible PET radiotracers for 5HT7. Three-dimensional pharmacophore evaluation/docking studies was performed to confirm its high affinity for 5-HT7 in comparison to 5-HT1A. Results: Two PET ligands, [ 11 C] ABO and [ 11 C] ABT, were successfully radiolabeled having radiochemical yield 25% ± 7% and 32% ± 4% (decay-corrected) in 25 ± 12 min (n = 7). [ 11 C] ABO showed better prospect because of more reversible tracer kinetics, once blocked with 10 µM cold ligands or with SB-269970 (67%-84% blocking in [ 11 C]ABO and 52%-75% in [ 11 C] ABT). Preliminary PET study in rat brain showed fast accumulation of radioactivity in the brain much higher for [ 11 C] ABO, 2.75 standardized uptake value (SUV) in comparison to [ 11 C] ABT, 1.73 SUV. Conclusion: In summary, these data indicated that arylpiperazinyl-alkyl benzoxazolone/benzothiazolone is promising skeleton to design PET ligand for 5-HT7, further optimization and longitudinal studies may lead to first small molecule-based PET ligand for 5-HT7 in clinics.
Nucleolipid nanoassemblies as novel molecular imaging probe-synthesis, theoretical insight, and preclinical evaluation of uridine nucleolipid derivative using single-photon emission computed tomography
Swastika Mishra, Shubhra Chaturvedi 1 , Preeti Jha 1 , Ankur Kaul 1 , B. Singh 2 , Anil Kumar Mishra 1
1 Division of Cyclotron and Radiopharmaceutical Sciences, Institute of Nuclear Medicine and Allied Sciences, New Delhi, 2 Department of Chemistry, Banaras Hindu University, Varanasi, Uttar Pradesh, India
Objective: Nucleosides have been used as bio-vectors for targeted molecular imaging agents but suffer challenges in cellular permeability. A lipophilic moiety covalently tethered to the nucleoside can help in improving cellular uptake. The polar head (nucleobase) and the lipophilic tail (lipidic chain) resemble membrane structure, thereby facilitating entry. Nucleolipid (NL) is also capable of assembling in the nano-size range (nano-sized particle [NP]). Proper design can provide site for radiolabeling, thereby developing NL as theranostic agents. When diethylenetriaminepentaacetic acid (DTPA) conjugated, these NPs can be labeled with metallic radionuclides ( 99m Tc and 68 Ga). Earlier, NL-DTPA has been reported as tumor imaging agent. In this work, NL-DTPA as nano-formulation (NPNL-DTP) is being evaluated for radiolabeling efficiency and targeting. Materials and Methods: Uridine appended with 16-hentriacontanone at 2'-3' was used for synthesizing NPNL-DTP. The amine functionalized 5' was conjugated to DTPA. Compounds were characterized. Molecular dynamics (MD) of NL-DTPA was performed. NPNL-DTPA were synthesized and studied for physicochemical properties and stability. Sulforhodamine B and MTT cytotoxicity assays were carried on HEK cell line. Characterization with TEM, radiolabeling of the NPNL-DTPA along are underway. Results: The yield of NL-DTPA was ≈85% and m/z at 1050. MD simulation of NL-DTPA showed a flip-flop mechanism of entry through the cellular membrane. Cytotoxicity studies of NPNL-DTPA indicate no appreciable toxicity up to 72 h. DLS showed size of 220 nm (PDI-0.309). The ζ-potential of −7.05 mV indicates that NPNL-DTPA were stable. Storing NPNL-DTPA at 4°C and 25°C did not cause any appreciable change in size, further indicating their stability. Conclusion: The studies show that NL-DTPA forms nanoparticles in desirable size range with good stability. NPNL-DTPA are designed to chelate metallic radionuclides and can be developed as efficient drug delivery systems with imaging capability.
Optimization of in-house synthesis of 68 Ga-ethylenediaminetetraacetic acid for glomerular filtration rate estimation by positron emission tomography and plasma sampling method
Ashish Kumar Jha, M. Sneha, Pradip Chaudhari, Bhabani Shankar Mohanty, Nilendu C. Purandare, Archi Agrawal, Sneha Shah, Venkatesh Rangarajan
Tata Memorial Hospital, Parel, Mumbai, Maharashtra, India
Objective: 99m Tc-diethylenetriamine penta acetic acid ( 99m Tc-DTPA) is used to estimate glomerular filtration rate (GFR) by gamma camera method. However, plasma sampling method of GFR estimation is considered as gold standard in clinical practice. 51 Cr-ethylenediaminetetraacetic acid ( 51 Cr-EDTA) is an ideal tracer for GFR calculation by plasma sampling method. 68 Ga-EDTA can replace both radiopharmaceuticals as positron emission tomography (PET) imaging agent as well as plasma sampling agent. The aim of our study was to devise an in-house labeling method for 68 Ga-EDTA synthesis. Materials and Methods: 68 Ga-EDTA was synthesized by freshly prepared EDTA solution and freshly eluted 68 Ga in 5 ml 0.5 M HCl from Ga-68/Ge-68 Generator. 0.36 g EDTA is dissolved in 0.5 ml of 2.5 M sodium acetate buffer and transferred into reaction vial containing 68 Ga and mixed well. Preparation is incubated at room temperature for 10 min. Radiochemical purity (RCP) was performed within 20 min and 3 and 6 h after formulation using instant thin-layer chromatography paper as solid phase and Na-Citrate as mobile phase. Free 68Ga moves to solvent front and 68 Ga-EDTA complex remains at point of spotting. PET imaging of 3 Swiss mice was also performed on FLEX Triumph PET/computed tomography (preclinical imaging system) after administration of 2-2.5 MBq of 68 Ga-EDTA at 2, 5, and 10 min after injection. Acquired data were reconstructed and images were analyzed visually and quantitatively. Results: 68 Ga-EDTA was formulated 23 times and quality control was performed. The average RCP within 20 min and 3 and 6 h of formulation was 98.86% ± 0.39%, 99.20% ± 0.37%, and 98.81% ± 0.31%, respectively. Visual interpretation of 68 Ga-EDTA images of mouse shows good excretion of tracer by kidney. The ratio of activity concentration in kidney and bladder at 2, 5, and 10 min were 5.2189, 0.1157, and 0.0322, respectively. Conclusion: Excellent RCP of 68 Ga-EDTA formulation up to 6 h and good excretion of tracer from kidney shows the reliability of in-house synthesis of 68 Ga-EDTA.
11 C-labeled naphthyl benzoxazolone derivative as positron emission tomography imaging probe for locating activated microglia in ischemic rat brain
Neelam Kumar, Ankur Kaul, Sunita Bhagat 1 , Anjani K. Tiwari 1
Division of Cyclotron and Radiopharmaceutical Sciences, Institute of Nuclear Medicine and Allied Sciences, Defence Research and Development Organization, 1 Department of Chemistry, Organic Synthesis Research Laboratory, ARSD College, University of Delhi, New Delhi, India
Objective: Translocator protein (TSPO) previously called as peripheral benzodiazepine receptor (PBR) has been considered as an efficient biomarker to trace the area of neuroinflammation in case of brain injury or any kind of neuropsychiatric disorders. Quantification of TSPO density in a specific region helps in monitoring the progression of disease. Initially, PBR and central benzodiazepine receptor (CBR) were considered as a single class of benzodiazepine receptor, but in late 90s, both receptors were considered as two different classes. Hence, it is a challenging task to design the ligand specific for PBR (TSPO). Herein, we are reporting the synthesis, computational, and biological evaluation of a potential 11 C-labeled ligand MNOP for positron emission tomography (PET) imaging in ischemic rat brain for TSPO. Methods: Proposed ligand was synthesized in six high yielding steps. In silico studies were performed and analyzed before proceeding for synthesis. In silico results are further supported by in vitro assays. In vitro autoradiography studies on ischemic rat brain were also carried to check the specificity and affinity of the designed radiolabeled ligand for TSPO receptor. Results: Computational GScore for MNOP indicated the higher affinity of ligand for the TSPO. Synthesis of MNOP was well characterized by spectroscopic techniques (Fourier transform infrared, nuclear magnetic resonance, and high-resolution mass spectrometry). In vitro binding assay showed high binding affinity Ki = 8.1 + 0.8 for TSPO over CBR Ki >100. To determine specific binding of [ 11 C] MNOP for TSPO, in vitro autoradiography was performed in ischemic rat model. ARG indicated significantly increased binding on the ipsilateral side compared with that on the contralateral side of ischemic rat brains. Conclusion: In summary, [ 11 C]-MNOP is a potential PET imaging agent, and in future, applicability of these ligands will be analyzed for microglial activation.
Utility of prostate-specific membrane antigen ligands for radionuclide imaging and therapy of prostate cancer
Chanchala Umesh Kale, Anil Parab, Laxman Khande, Parag Aland, V. R. Lele
Nuclear Medicine and Positron Emission Tomography-Computed Tomography Department, Jaslok Hospital and Research Center, Mumbai, Maharashtra, India
Objective: To synthesize and to study potential for prostate-specific membrane antigen (PSMA) ligands for diagnostic and therapeutic purpose. Methods: PSMA (HBED-CC), product name PSMA-11 and PSMA DOTA conjugate, product name PSMA-617 were used for labeling with 68 Ga (diagnostic) and 177 Lu (therapeutic), respectively. 177 Lu, LuCl3, is easily available in India. Preparation of 68 Ga-PSMA: 2 ml of 68 Ga-Cl3 radioactivity, obtained from 68 Ge- 68 Ga generator, was added to reaction vial containing 200 mg sodium acetate buffer and 7-10 µl PSMA-11 and heated for 10 min at 900°C. This solution was filtered through C-18 Sep-Pak cartridge and eluted with 0.5 ml 50% ethanol. A volume of 10 ml NaCl was added for dilution. Patient dose of 2-5 mCi was filtered through 0.22 um sterile filter before injecting to patients. A routine positron emission tomography-computed tomography (PET-CT) scan was done at 50-70 min later. For preparation of patient dose of 177 Lu-labeled PSMA-617, a stock solution of PSMA-617 was prepared by dissolving 1 mg (0.96 µmol) of ligand to 1 ml supra pure water. A 50-100 µl aliquot mixed with 700-800 µl of ascorbic acid buffer (pH 5) solution was added 177-LuCl3 (100-200 µl, specific activity 20-30 mCi/g, 80-200 mCi) at 950°C for 15 min. The radiopharmaceutical purity of 177 Lu-PSMA 617 was checked by instant thin-layer chromatography method and found to be >97%. Eleven patients (age 48-81 years mean: 64.5) underwent Lu-177 PSMA therapy (dose 80-200 mCi). Posttherapy scan on gamma camera was performed at 20 h. The images were congruent with 68 Ga-PSMA images. Results: (1) Intense uptake was found in metastatic bone lesions, lymph nodes, etc. (2) All lesions, which were seen in 68Ga PSMA-11 PET-CT scan, showed the uptake of 177 Lu-PSMA 617 in all patients. Conclusion: Using PSMA-HBED-Cc (PSMA 11) and PSMA-617 for the diagnosis and therapy, respectively, is cost-effective and convenient method for treatment of prostate cancer patients. Hence, this pair of PSMA ligand poses good potential for the management of prostate cancer.
Design, synthesis, preliminary evaluation of [ 99m Tc-DTC-MPP-BTZ] complex: A novel single-photon emission computed tomography neuroimaging agent for 5-HT1AR/5-HT7R dimeric complexes
Preeti Jha, Shubhra Chaturvedi, Swastika Mishra, Nidhi Jain, and Anil K. Mishra
Department of Cyclotron and Radiopharmaceutical Sciences, INMAS, DRDO, New Delhi, India
Objective: Serotonin (5-HTR) receptors, 5-HT1AR and 5-HT7R, are implicated in neurological disorders. 5-HT7R is a modulator for 5-HT1AR and the formation of 5-HT1AR/5-HT7R complex is one of the mechanisms for inactivation and desensitization of 5-HT1AR. These are highly co-expressed in brain regions as heterodimers and represent an important pharmacological target for the treatment of depression and anxiety. Imaging of 5-HT1AR/5-HT7R complex can be utilized to assess the quantitative and functional aspect of neurological disorders. In this study, 5-HT1AR/5-HT7R dimers are mapped using methoxyphenylpiperazine-benzothiazolone (MPP-BTZ) mixed pharmacophore. The MPP-BTZ was modified as dithiocarbamate (DTC-MPP-BTZ) and then 99m Tc-radiolabeled followed by in vivo validation. Methods: Synthesis involved conjugation of MPP and BTZ, followed by functionalization of a secondary amine with dithiocarbamate. Intermediates and final compound were characterized by analytical methods. DTC-MPP-BTZ was 99m Tc-radiolabeled with optimization of various parameters. [ 99m Tc-DTC-MPP-BTZ] complex was evaluated for stability, lipophilicity, biodistribution pattern, and validated through SPECT imaging. Results: The yield of DTC-MPP-BTZ (m/z 503) was 95%. Results indicated excellent radiolabeling, >98% at pH 6.5. The radiolabeled complex was found stable in serum. The logP complex was −0.26 at pH 7.4, which ensures the optimum lipophilicity to cross blood-brain barrier. Brain uptake was 1.3% ID/g and complex showed hepatobiliary route of excretion. Regional brain uptake indicated 76% localization of the brain radioactivity in the hippocampus region. Conclusion: Novel single-photon emission computed tomography imaging agent to target 5-HT1AR/5-HT7R complex was synthesized using mixed pharmacophore MPP-BTZ and modified with DTC as DTC-MPP-BTZ. The accumulation in the 5-HT-specific regions (hippocampus), excellent radiolabeling, and pharmacological properties make 99m Tc-DTC-MPP-BTZ a promising candidate for central nervous system imaging.
Design, synthesis, and evaluation of novel fluorine-18 positron emission tomography tracer in diagnosis of Alzheimer's disease
Arun M. Bhusari, N. Lakshminarayanan, Yogita P. Pawar, Surendra H. Moghe, Harikesh N. Janmanchi, Mariam S. Degani, M. G. R. Rajan, S. Banerjee
Radiation Medicine Centre, BARC, TMH Annexe, Parel, Mumbai, Maharashtra, India
Objectives: The aim was to design suitable target molecules that can interact with amyloid beta (Ab) fibrils, with suitable blood-brain barrier (BBB) penetration properties; screening and synthesis of these molecules for Ab fibril binding property; synthesis of suitable precursor molecule and labeling with F-18 and purification of the highly active molecule; and ex vivo and in vivo biodistribution of (F-18)-labeled molecule in animal - preclinical studies. Materials and Methods: Screening of molecules was based on ligand-based drug design (LBDD) and structure-based drug design (SBDD) studies performed using computational drug design modules. The designed molecules were synthesized via cold fluorination and characterized by spectroscopy. The logP values of molecules were determined using HPLC. Molecules were screened for binding to Ab fibrils using thioflavin T (ThT) assay. The precursor of most active molecule was (F-18) radiofluorinated and purified by chromatography. The ex vivo and in vivo biodistribution was studied in Wistar rats and New Zealand white rabbits, respectively. Results and Discussion : Theoretical studies on the designed molecules showed alignment and pharmacophoric elements similar to that of reported Ab plaque-binding molecules. The experimentally calculated logP values were similar to the predicted values. In ThT assay, one of the fluorinated molecules showed best binding potential. The radiofluorination yield for the precursor of the most active molecule was >70%. The radiolabeled molecule showed good BBB penetration in Wistar rat and New Zealand White rabbit. Conclusions: LBDD and SBDD study assisted in the understanding of the molecules necessary for binding to Ab fibrils. In vitro studies investigated the potential of the ligand for Ab fibrils binding. Ex vivo and in vivo biodistribution of radiolabeled molecule in animals showed good BBB penetration property, thereby showing that the molecule designed can be used for diagnosis of AD.
Radiolabeling of tamoxifen using Tc-99m tricarbonyl core
Anupriya, Jaya Shukla, Priya Bhusari, Rakhee Vatsa, Kanchan, B. R. Mittal
Department of Nuclear Medicine, Postgraduate Institute of Medical Education and Research, Chandigarh, India
Introduction: Tamoxifen is a selective estrogen receptor modulator, which has been approved by the Food and Drug Administration for the treatment of estrogen receptor-positive breast cancers. Radiolabeled tricarbonyl complexes have wide variety of applications in diagnosis and therapy. This study aimed to radiolabel tamoxifen with Tc-99m via tricarbonyl complex as a diagnostic radiopharmaceutical for estrogen receptor-positive breast cancers. Materials and Methods: Sodium boranocarbonate (carbon monoxide producing source) was dissolved in 0.1 M phosphate-buffered saline (pH = 7.5) and 5 mCi of Tc-99m was added. The total volume of reaction mixture was kept 1 ml and was incubated at 100°C for 30 min in water bath. Reaction mixture was cooled followed by quality control using saline, acetone, and methanol:HCl (99:1) as mobile phase. Tamoxifen (5 mg) was added to the carbonyl solution and incubated at 95°C for 30 min at various pH values (3.5, 6, and 7.5). Quality control was done with instant thin-layer chromatography using methanol:HCl (99:1) as solvent. Further, to rule out the presence of free technetium-99m, 0.1 ml Tc-99m tricarbonyl mixture was incubated with 0.05 M ethylenediaminetetraacetic acid (EDTA) without adding tamoxifen. Results: The Rf of Tc-99m tricarbonyl complex and Tc-99m-tricarbonyl-tamoxifen complex was 0.3 and 0.4, respectively, in methanol:HCl (99:1). In saline, the peak of Tc-99m-tricarbonyl-tamoxifen complex was observed at the base (due to hydrophobic nature of tamoxifen). The peak of EDTA-containing Tc-99m tricarbonyl was observed at the solvent front with acetone and saline, thus confirming the formation of tricarbonyl core and absence of free technetium-99m. The radiolabeling efficiency was found to be >98% at all pH values (3.5, 6, and 7.5). Conclusion: Tc-99m-tricarbonyl core can be prepared in-house, and tamoxifen can be labeled using Tc-99m-tricarbonyl core for using as an imaging agent for ER+ breast cancer.
Optimization of in-house formulation of 68 Ga-macroaggregated albumin using commercially available macroaggregated albumin cold kit
Sneha Mithun, Ashish K. Jha, Pradip Chaudhari, Bhabani Shankar Mohanty, Sharada Sawant, Nilendu C. Purandare, Archi Agrawal, Sneha Shah, Venkatesh Rangarajan
Tata Memorial Hospital, Parel, Mumbai, Maharashtra, India
Objective: 99m Tc-macroaggregated albumin (MAA) is used for lung perfusion using gamma camera. The aim of our work is to optimize labeling of 68 Ga-MAA using commercially available MAA cold kit as a positron emission tomography (PET) alternative to 99m Tc-MAA. Materials and Methods: Commercially available GMP certified cold kit for 99m Tc labeling was used, which contains 2.5 mg MAA (4-5 million particles; 20-40 µm), 5.0 mg albumin human, 0.1 mg SnCl 2 dehydrate, and 1.2 mg NaCl. MAA particles were separated from SnCl 2 and albumin by centrifugation at 3000 rpm for 2 min. 68 Ga was eluted from GMP compliant 68 Ga/ 68 Ge generator using 0.05 M HCl into a reaction vial, to which were added 2.5 M sodium acetate buffer to titrate the mixture to pH 3.5-4.5 and MAA particles followed by vigorous stirring. The vial was heated in water bath at 85°C for 20 min agitating continuously using vortexer to prevent sedimentation. Radiochemical purity (RCP) of the product was determined by instant thin-layer chromatography using instant thin-layer chromatography (ITLC) paper and sodium citrate buffer (mobile phase). The particle size was determined by transmission electron microscopy. Positron emission tomography (PET) imaging of 3 Swiss mice was performed using FLEX Triumph PET/computed tomography (CT) (preclinical imaging system) at 10, 15, 25, 45, and 50 min after administration of 0.5-1.2 MBq freshly prepared 68 Ga-MAA. Results: 68 Ga-MAA labeling and ITLC were performed 30 times. Mean RCP was 98.7% and pH 3.5-4.5. Average particle size from three different preparations was 20-80 µ. PET/CT images of Swiss Mice showed accumulation of tracer in the lungs, and there was no tracer accumulation noted in the rest of the body. Approximately 99.9% trace accumulation was noted in the lung. Conclusion: More than 95% RCP of 68 Ga-MAA and accumulation of the radiopharmaceutical principally in the lungs of mouse proves the reliability of in-house formulation of 68Ga-MAA.
| Dosimetry and Radiation Safety|| |
How secure occupational radiation workers during 18 F-fluorodeoxyglucose synthesis
Sandeep Singh, Shrishti Varma, Sarita Kumari, Subhash C. Kheruka, Ramesh Chandra, Manish Dixit, Sanjay Gambhir
Department of Nuclear Medicine, SGPGIMS, Lucknow, Uttar Pradesh, India
Introduction: Radiation monitoring is needed and mandatory scientific protocol for nuclear medicine facility to measure and analyze the data. These data are helpful in designing the course of work as well as required monitor the absorbed dose from radiation exposure during routine duties. There are guidelines and recommendation via regulatory authority such as IAEA, AERB, and NRC on safety and precautions during radiation work performed by the occupational workers. The main purpose of this work is to measure and record the radiation exposure of occupational worker during production of (18 F)-fluorodeoxyglucose (FDG), dose dispensing, and its quality control. Materials and Methods: Personal radiation monitoring during (18 F)-FDG synthesis was performed daily basis using warm thermoluminescent dosimetry badge and using (Radimage Cs-137 crystal) pocket dosimeter. Monitoring was done during synthesis, dose dispensing (3000 mBq/6 ml), and transferring via pneumatic shoot (8 m distance from dispenser) and quality control tests (352 µCi) such as R-thin-layer chromatography, pH, gas chromatography, endotoxin, filter integrity test, and HPLC. Results: The contribution of each stage to the total occupational dose during production of (18 F)-FDG was analyzed separately: at the time of automated synthesis, it was 0 mR, and at the time of dose dispensing, the mean value was approximately 1.83 mR; during quality control, it was approximately 0.83 mR; and finally, during overall performance of the synthesis protocol, the radiation dose was 2.66 mR. Conclusion: The result showed the total absorbed dose of occupational workers within limits as recommended by regulatory authority.
Challenges in setting-up and operating Nuclear Medicine Department in India: How to overcome them
Hasmukhkumar Jain, Sachin Gawde
Mumbai Institute of Nuclear Theranostics, Dhanvantari Hospital, Navi Mumbai, Maharashtra, India
Objective: Growth of Nuclear Medicine (NM) in India is not at par with that of the developed countries such as the USA, the UK, Germany, Italy, France, and Japan. Thus, there is a need to have a critical analysis of the hiccups in setting-up a NM Department in India with possible ways to overcome them. Core Issues: There are various challenges that need to be taken into consideration before going ahead with setting-up a new NM Department within the country. They are as follows: (1) challenges in site identification, (2) challenges in designing the layout, (3) challenges in infrastructure construction, (4) challenges in selection of machines, (5) challenges in appointment of qualified staff, (6) challenges during AERB inspection, and (7) challenges in smooth operation of the NM Department. (a) Electricity supply, (b) machine breakdown, (c) trained engineers, (d) radioisotopes, (e) cold-kits, (f) PACS and telemedicine, (g) printers, cartridges, stationery, etc., and (h) radiation monitoring instruments. Conclusion: Opening a new NM Department in India is not possible without difficulties, but with careful site selection, design planning, construction, purchase of right equipment and accessories with provision of uninterrupted power supply, ensuring regular supply of radioisotopes, and cold-kits with the help of qualified staff, one can meticulously plan and execute the process smoothly. However, adequate time and money needs to be kept at hand to avoid glitches in the later phase of the development of NM Department.
| Endocrinology|| |
Comparison of multi-time-point 99m Tc sestamibi/ 99m Tc pertechnetate parathyroid planar scan with conventional dual-time-point scans through interobserver agreement: A kappa analysis
Latika Kathayat, Natasha Singh, Madhuri Shimpi Mahajan, Umesh Mehta, Tattwamasi Bharadwaj
Department of Nuclear Medicine, P. D. Hinduja National Hospital and MRC, Mumbai, Maharshtra, India
Objective: Parathyroid lesions (10%-15%) show early washout of Tc-sestamibi tracer by 1-1.5 h, in which case dual phase imaging yields false negative results. Here, we validate the advantage of multi-time-point scans as compared to dual-time-point scans through interobserver agreement. Methods: Eighty patients referred for a parathyroid scan to localize parathyroid adenoma were included in this study. 15 mCi of 99m Tc-sestamibi was injected and static images were obtained at 5, 20, 30, 45 min and 1 and 2 h and if required 3 h images were obtained. Subsequently, 5 mCi of Tc-99m pertechnetate was injected and thyroid images were obtained at 20 min after injection. All images were obtained in GE Infinia Hawkey. The images were grouped into two sets: one containing the images at all-time points and the other containing images at 20 min and 2 h (dual time point). The images were randomized, interpreted by four independent nuclear medicine physicians with regard to whether the suspected parathyroid lesion was present/absent. The interobserver agreement was assessed with Fleiss kappa for four observers. Results: Fleiss kappa analysis for interobserver agreement revealed 0.7041 SE (substantial agreement) for multi-time-point images and 0.6081 SE (moderate agreement) for dual-time-point images. Five patients with a negative scan on dual-time-point images were found positive by one or more observers on multi-time-point images, of which three patients were found positive on histopathology and rest have shown biochemical confirmation of parathyroid adenoma and are awaiting for the surgery. Conclusion: Our study validates improvement in interobserver agreement when multi-time-point images were used, and also it reduces the number of false negative cases as elucidated in above cases. This protocol shall prove to be a boon in centers lacking single-photon emission computed tomography/computed tomography facility; however, further studies with larger subject population are suggested to confirm further our observations.
| Genitourinary system|| |
Assessment of optimal time to perform counting for glomerular filtration rate evaluation by plasma sampling method
Manoj Kumar H. Chauhan, Ashish Kumar Jha, M. Sneha, Nilendu C. Purandare, Archi Agrawal, Sneha Shah, Venkatesh Rangarajan
Tata Memorial Hospital, Mumbai, Maharshtra, India
Objective: Glomerular filtration rate (GFR) is used to assess overall function of kidney in various nephrological and urological conditions. GFR measurement by serum creatinine and gamma camera method are routinely used. Plasma sampling method is considered gold standard for GFR estimation. Plasma sampling method estimates accurate GFR but it is time consuming and requires expertise to perform. The aim of our study is to find the optimal timing to perform counting. Methods: Fifteen patients (male: 11 and female: 4; average age: 43 years) who underwent GFR evaluation by plasma sampling method (two-sample) were included in this study. Patients were advised to drink 250 ml water half an hour before dose administration. Age, sex, height, and weight of patients were noted. Standard and patient dose of 2.5-3 mCi of 99m Tc-diethylenetriaminepentaacetic acid (DTPA) were prepared in separate syringes. Pre- and post-injection, weight of patients, and standard syringes were measured using precision balance and noted. Standard was dissolved in 1000 ml water. Injection was performed using scalp needle and followed immediately by 20 ml of normal saline chase. Two plasma samples were collected from the contra lateral arm at 2 h and 4 h postadministration of 99m Tc-DTPA. Plasma samples and standard were pipetted in duplicate and counted. Counts were obtained 4, 12, and 24 h after collection of the second plasma sample. GFR was estimated using in-house developed GFR calculation software. All three sets of data were statistically analyzed for correlation. Results: The average GFR estimated for 4, 12, and 24 h counting were 37.02 ± 31.45, 47.62 ± 33.48, 49.77 ± 33.49, respectively. GFR value for 12 h counting and 24 h counting had better correlation (correlation coefficient = 0.999) compared to 4 h counting GFR value, which were systematically low. Conclusion: Our study shows that 12 h is the optimal time for counting the sample for GFR estimation by plasma sampling method if higher activity of 99m Tc-DTPA is administered.
| Cardiology|| |
Role of 18 F-fluorodeoxyglucose cardiac positron emission tomography and 99m Tc-sestamibi myocardial perfusion imaging in assessing the therapeutic benefit in patients with coronary artery disease and left ventricular systolic dysfunction
Ankur Pruthi, Promila Pankaj, Rajneesh Jain, Ritu Verma
Department of Nuclear Medicine and Positron Emission Tomography-Computed Tomography, Mahajan Imaging Centre, Sir Ganga Ram Hospital, New Delhi, India
Objective: To evaluate the therapeutic benefit with "revascularization" and "optimal medical treatment (OMT)" in patients diagnosed with hibernating myocardium on myocardial viability imaging using F-18 fluorodeoxyglucose cardiac positron emission tomography. Methods: Fifty-nine consecutive patients (43 males, 16 females, mean age 60.7 ± 9.4 years) with coronary artery disease (CAD) and left ventricular (LV) systolic dysfunction who underwent myocardial viability imaging for revascularization workup and were diagnosed with hibernating myocardium were enrolled in this study. Patients were later treated with either revascularization or OMT and were followed for a median duration of 7.7 months for assessing the therapeutic benefit. Therapeutic benefit was assessed under three categories: (a) improvement in functional class, (b) adverse cardiac events, and (c) improvement in LV function and myocardial perfusion on follow-up resting 99m Tc-sestamibi myocardial perfusion imaging (MPI). Results: Twenty-nine patients underwent revascularization (49%) and 25 patients received OMT (42%). Five patients were lost to follow-up. Patients were matched for baseline characteristics in both treatment arms. On follow-up, significant improvement was noted in the New York Heart Association functional class and the Canadian Cardiovascular Society angina class postrevascularization. No such improvement was noted in the OMT group. The cardiac event rate of patients in OMT group was significantly higher than that of patients in revascularization group (36% vs. 10.3%; P = 0.046). At 1-year follow-up, event-free survival in revascularization group was significantly superior compared to OMT group (83.8% vs. 50.8%; P = 0.039). On follow-up resting MPI scan, mean improvement in LVEF in revascularization group was significantly higher than in OMT group (6.0% vs. 1.4%; P = 0.04). Conclusion: Myocardial viability imaging is a sensitive modality to identify hibernating myocardium in patients with CAD and LV dysfunction and predicting its recovery following revascularization, thereby guiding the optimal treatment strategy for these patients.
| Brain Imaging|| |
F-18 fluorodeoxyglucose positron emission tomography patterns in autoimmune encephalitis
Divya Yadav 1,2 , Madhavi Tripathi 1,2 , Manjari Tripathi 1,2 , Deepa Dash 1,2 , Kavish Ihtisham 1,2 , S. T. Arun Raj 1,2 , Nishikant A. Damle 1,2 , Shamim A. Shamim 1,2 , Chandrasekhar Bal 1,2
Departments of 1 Nuclear Medicine and 2 Neurology, CN Centre, AIIMS, New Delhi, India
Objective: Autoimmune encephalitis (AIE) is a clinically challenging diagnosis. With emerging evidence of reversibility with immunotherapy, early diagnosis is crucial. The utility of F-18 fluorodeoxyglucose (FDG) positron emission tomography (PET) in the diagnosis and monitoring of AIE has been found significant despite an unremarkable magnetic resonance imaging (MRI). We present the patterns of metabolism on FDG PET in AIE evaluated in our department. Methods: Twenty patients (12 males and 8 females), mean age (±standard deviation) = 32 (23.5) years, undergoing workup for AIE underwent F-18 FDG PET as per the standardized protocol. Each PET study was visually evaluated for the presence of hypometabolism or hypermetabolism and its spatial distribution pattern noted. These patterns were then correlated with the antibody positivity and MRI brain. The antibody profile was as follows: NMDA positive = 11 cases, LGI1 positive = 2, CASPR2 positive = 1, VGKC positive = 1, GAD positive = 4, and AMP AR2 positive = 1. Results: The followings were the spatial patterns of metabolism noted for those with NMDA antibodies: hypermetabolism in mesial temporal cortices, basal ganglia, and midbrain with hypometabolism in the occipital cortices. VGKC antibodies including LGI1 and CASPR2 corresponded with hypermetabolism in the basal ganglia. In one case with LGI1, hypermetabolism was prominent in both superior temporal gyri with a ribbon-like pattern. Patients with anti-GAD positivity had basal ganglia and mesial temporal hypermetabolism with hypometabolism in the parietotemporal and cerebellar cortices. MRI showed signal alterations in the form of mesial temporal hyperintensities in only five of these patients. Conclusion: FDG-PET is a useful tool in the diagnostic workup of AIE with characteristic metabolic patterns. Recognition of these imaging patterns is essential for appropriate interpretation of the FDG-PET scans in these patients. In cases with a normal MRI, FDG-PET can be positive, thus providing crucial evidence for institution of timely therapy.
| Radionuclide Therapy|| |
To evaluate the effectiveness of single-dose recombinant human thyrotropin injection in posttotal thyroidectomy patients in differentiated thyroid cancer: Our experience
Julie Hephzibah, David Mathew, Nylla Shanthly, Regi Oommen
Department of Nuclear Medicine, Christian Medical College, Vellore, Tamil Nadu, India
Objective: Differentiated thyroid cancers are thyrotropin (TSH)-dependent tumors. To detect remnant or metastatic lesions in posttotal thyroidectomy patients, recombinant human thyrotropin (rhTSH) is being used as a better alternative to levothyroxine withdrawal for stimulated diagnostic thyroid whole-body scan (TWBS) and radioactive iodine ablation/therapy. The current protocol is two doses of rhTSH (0.9 ml IM) on day 1 and day 2. TWBS dose is given on day 3, followed by TWBS on day 5. Two similar doses of rhTSH is given followed by remnant ablation/therapy. The aim of this study was to document the effectiveness of a single rTSH dose for both diagnostic scan and ablation without compromising on patient care. Methods: We analyzed patients who underwent rhTSH-stimulated TWBS and treatment from 2011 to 2016. A total of 18 patients (23 injections) underwent single-dose rhTSH injection on day 1, followed by TSH, serum thyroglobulin estimation, and TWBS dose on day 2. TWBS was done on day 3, i.e., in 24 h followed by RAIA on the same day if indicated. Seventeen patients underwent RAIA, one patient underwent twice. Posttherapy scan was done 48-96 h following discharge. Results: There were 4 males and 14 females, age range 30-77 years. Mean TSH levels 24 h after rhTSH administration was 132 mIU/ml. Twelve TWBSs showed remnant thyroid, one negative and five showed functional metastases. All 17 posttherapy scans showed good uptake in thyroid bed or in metastatic lesions. Exposure rates measured at 24 h after ablative dose at 1 m distance were comparable with randomly chosen controls matched for age, sex, and disease stage. Conclusion: Single-dose rhTSH is a novel method instead of levothyroxine withdrawal for stimulated thyroglobulin, TWBS, and RAIA. It is time saving, overcomes a month long waiting, and combats morbidity associated with hypothyroidism. This protocol has proven to be a cost-effective alternative for patients undergoing diagnostic scan and remnant ablation/therapy.
Peptide receptor radionuclide therapy in metastatic/advanced medullary thyroid carcinoma expressing somatostatin receptors: A clinical efficacy assessment
Rahul Vithalrao Parghane, China Naik, Sandip Basu, Sharmila Banerjee
Radiation Medicine Centre (Bhabha Atomic Research Centre), TMH, Mumbai, Maharashtra, India
Objective: The aims of this study were to evaluate the response rate by improvement in clinical symptomatology, biochemically, and objective response using molecular and structural imaging in metastatic medullary thyroid carcinoma (MTC) following 177 Lu-DOTA-TATE-based peptide receptor radionuclide therapy (PRRT). Materials and Methods: A total of 23 patients (3 women, 20 men; median age 48 years, range 25-80 years) with metastatic or advanced MTC were included and analyzed retrospectively for PRRT response evaluation in this study. 177 Lu-DOTA-TATE was administered using the standard PRRT protocol with amino acid-based renal protection with 150 mCi/cycle, and cycles were repeated at intervals of 12-16 weeks (range 1-6 cycles, average 3 cycles). The posttreatment response evaluation includes 68 Ga-DOTA-TATE positron emission tomography-computed tomography (PET-CT) and 18 F-FDG PET-CT in all patients, and they were also evaluated for symptomatic and biochemical responses (serum calcitonin). These patients were classified as responders (response rate) and nonresponders using predefined response criteria. Results: Of the 23 patients, 5 patients (22%) died and 18 patients (78%) were alive at the time of analysis of this study with follow-up range from 6 to 50 months (average 22 months) after first PRRT. Of 23 patients, 13 patients (57%) were overall responders to PRRT and 10 patients (43%) were overall nonresponders, based upon response assessment by clinical symptomatic, biochemical, and objective imaging response criteria. All patients had well-tolerated PRRT procedures; there was no major hematological and renal toxicity in any of these 23 patients. Conclusions: PRRT with 177 Lu-DOTA-TATE-based therapy seems to be have a definite role in patients with metastatic and advanced MTC having somatostatin receptor-positive lesions in stabilizing the disease and to improving the quality of life in these patients. PRRT is a promising therapeutic tool with minimal toxicity in metastatic and advanced MTC as compared to other therapeutic options.
To evaluate the role of lutetium-177 tin colloid radiosynovectomy in patients with inflammatory knee joint conditions who are nonresponders of conventional modalities
Pragati Jha, Shamim Ahmed Shamim, Tahir M. Ansari,
Uma Kumar, Surabhi Vyas, Manoranjan Singh, Sanjan Ballal, Madhav Yadav, Deepak Gautam, Chandrasekhar Bal
Department of Nuclear Medicine, Thyroid Clinic, AIIMS, New Delhi, India
Aim: To evaluate the role of lutetium-177 (Lu-177) tin colloid radiosynovectomy (RSV) in patients with inflammatory knee joint conditions who are not responding to conventional modalities in a setup where Re-188 and Y-90 are not available. Materials and Methods: In this prospective study, 26 knee joints in 24 patients with chronic synovitis due to different inflammatory knee joint conditions not responding to conventional therapy underwent RSV. Patients were assessed clinically for pain, swelling, tenderness, joint mobility, analgesic use, and on bone scan (blood pool). Different scores were given to all these clinical parameters. RSV of knee joint was done using intra-articular injection of 370-740 MBq of Lu-177 tin colloid. Treatment response was assessed at 3-12 months with various clinical parameter scores and dynamic bone scan. Patients were categorized as responders and nonresponders on the basis of change in percentage of clinical scores and change in blood pool activity. Results: Of 26 joints, 13 were responders and 13 were nonresponders at 3-12 months post-RSV. There was a statistically significant reduction in clinical parameters cumulative scores on follow-up when compared with baseline in responder group. In addition, there was significant reduction in blood pool activity in responder when compared with the baseline. Patients injected higher dose responded better compared to those were injected less activity. Conclusion: Lu-177 tin colloid synovectomy can be used as treatment modality in patients with chronic inflammatory knee joint conditions who are not responding to conventional treatment in a setup where Re-188 and Y-90 are not available.
| Oncology|| |
Role of 68 Ga-prostate-specific membrane antigen positron emission tomography/computed tomography for evaluation of response to docetaxel chemotherapy in metastatic castration-resistant prostate cancer
Krishan Kant Agarwal 1,2,3 , Madhavi Tripathi 1,2,3 , Ranjit Sahoo 1,2,3 , Rajiv Kumar 1,2,3 , Chandrasekhar Bal 1,2,3
1 Department of Nuclear Medicine, Sterling Cancer Hospital, Ahmedabad, Gujarat, Departments of 2 Nuclear Medicine and 3 Medical Oncology, IRCH, All India Institutes of Medical Sciences, New Delhi, India
Objective: Glu-NH-CO-NH-Lys-(Ahx)-[Ga-68(HBED-CC)], abbreviated as 68 Ga-prostate-specific membrane antigen (PSMA), is a novel radiotracer undergoing evaluation for positron emission tomography/computed tomography (PET/CT) imaging of prostate carcinoma. Its major advantage is sensitive detection of lesions even at low prostate-specific antigen (PSA). The objective of this prospective study was to evaluate response to docetaxel chemotherapy (DCT) in metastatic castration-resistant prostate cancer (mCRPC) using 68 Ga-PSMA PET/CT. Methods: A total of 17 male patients (mean age - 62 ± 20) with mCRPC and rising PSA levels that had been planned for DCT were evaluated prospectively. All patients had undergone bilateral orchidectomy. The median PSA level was 88, range 4-1100 ng/mL, and mean Gleason score was 8.0 ± 1. Baseline 68 Ga-PSMA PET/CT was done in all patients followed by an interval PET/CT after 4 cycles DCT. Based on-response was graded as partial response (PR), stable disease (SD), and progressive disease (PD). In all cases, response was correlated to serum PSA levels. Results: Abnormal tracer accumulation suggestive of metastases was seen in retroperitoneal lymph nodes in 5 (29%) patients, pelvic lymph nodes in 9 (53%), skeletal sites in 11 (65%), internal mammary and supraclavicular lymph nodes in 3 (18%), and liver in 1 (5%), suggesting PSMA expression in baseline scan. PSMA expression was also noted in the primary in prostate in 5 (29%) patients. After DCT, 4 patients had PR (23%), 6 had SD (35%), and 7 patients showed PD (42%) in posttherapy 68Ga-PSMA scan. In all with PD, PSA levels were also found to rise with a new lesion on the Ga-68 PSMA PET/CT (28% rise in mean sPSA level). PR patients showed decline in PSA levels (up to 80% decreased in mean sPSA level). Conclusions: Thus, 68 Ga-PSMA PET/CT is a useful modality for evaluation of response to DCT in mCRPC patients, further these patients would also be suitable candidates for 177 Lu-PSMA therapy.
Role of various semiquantitative parameters of F-18-fludeoxyglucose positron emission tomography/computed tomography studies for interim treatment response evaluation in nonsmall cell lung cancer
Akshima Sharma, Anant Mohan, V. Sreenivas, Ashu Seith Bhalla, M. C. Sharma, Anil Kumar Pandey, Rakesh Kumar
Department of Nuclear Medicine, All India Institute of Medical Sciences, New Delhi, India
Objective: To prospectively evaluate the role of various semiquantitative parameters obtained from F-18-fludeoxyglucose positron emission tomography/computed tomography (F-18-FDG PET/CT) and to determine the best one for response assessment to chemotherapy in biopsy-proven nonsmall cell lung cancer (NSCLC) cases. Methods: Thirty-two patients (M/F = 25/7) with mean age 54.71 ± 12.65 years with biopsy-proven NSCLC (21 adenocarcinoma and 11 squamous cell carcinoma) were enrolled in the study. Each patient underwent baseline and post 4 cycle chemotherapy whole-body F18-FDG PET/CT scan after injecting 0.14-0.21 mCi/kg of F-18-FDG intravenous. Images were analyzed by two experienced nuclear medicine physicians and five PET/CT parameters were evaluated (target:background ratio [TBR], standardized uptake value [SUV]max, SUVmean, metabolic tumor volume [MTV]wb, and TLGwb) for both scans. The percentage changes (∆) of all parameters were also evaluated. Patients were divided into two response groups as per RECIST 1.1 criteria: responders (complete and partial response) and nonresponders (stable and progressive disease). All parameters were compared among two response groups using appropriate statistical methods, P < 0.05 was considered statistically significant. Results: Of 32 patients, 5 had Stage III and 27 had Stage IV disease at baseline evaluation. Sixteen patients were responders and 16 were nonresponders. All parameters evaluated in postchemotherapy scans were significantly higher in nonresponders as compared to that of responders (P < 0.05). Among the percentage changes of all parameters, 3 parameters (∆MTVwb, ∆TLGwb, and ∆SUVmax) were found to be significant in prediction of response. In receiver operating characteristic analysis, postchemo TBR and ∆MTVwb came out to be most accurate with area under the curve 0.83 and 0.81, respectively. In multivariate analysis, post-TBR and ∆MTVwb were found to be the two independent variables for response assessment. Conclusion: All the parameters in postchemotherapy scans and percentage changes in three parameters (∆MTVwb, ∆TLGwb, and ∆SUVmax) have significant role in prediction of response. Of these significant parameters, post-TBR and ∆MTVwb were able to predict the response more accurately.
Role of gray level co-occurrence matrices-based texture analysis using fludeoxyglucose positron emission tomography/computed tomography in evaluation of response to neoadjuvant chemohormonal therapy in locally advanced breast cancer
Ganesh Kumar, Anil Kumar Pandey, Rakesh Kumar
Department of Nuclear Medicine, AIIMS, Ansarinagar, New Delhi, India
Objective: Our study assesses the possible role of texture analysis in fludeoxyglucose positron emission tomography/computed tomography (FDG PET/CT) using gray level co-occurrence matrices (GLCM) in evaluation of response to neoadjuvant chemohormonal therapy for locally advanced breast cancer (LABC). Methods: Thirty female patients with histopathologically confirmed breast cancer were enrolled in this prospective study. Following completion of three cycles of neoadjuvant therapy, each patient underwent a posttherapy PET/CT. From each scan, the gray-scale image of that section of primary tumor with longest diameter was used to obtain the following GLCM-based texture parameters: angular second moment, inverse differential moment, contrast, entropy, and correlation. For comparison, routinely used metabolic parameters, namely, standardized uptake value (SUV)max, SUVmean, primary lesion metabolic tumor volume (MTV), and whole-body MTV, were obtained. Results were obtained with P < 0.05 considered statistically significant. Results: On test-retest reliability analysis, there was excellent linear and ranked correlation for all texture parameters. RECIST 1.1 criteria identified 16 responders (partial response = 15, complete response = 1) and 14 nonresponders (stable disease = 6, progressive disease = 8). On Mann-Whitney U-test, contrast and entropy were significantly different between responders and nonresponders (P < 0.0001). The percentage change between post- and pre-therapy value of each texture parameter was calculated and employed for receiver operating characteristic analysis in which entropy (area under curve [AUC] = 0.902) and contrast (AUC = 0.879) again outperformed the other parameters. SUVmean (AUC = 0.888), SUVmax (AUC = 0.857), and MTV (AUC = 0.821) also performed reasonably. Contrast, entropy, SUVmean, and SUVmax were used for logistic regression analysis to predict nonresponders. In the resulting model, only contrast was shown significant (P = 0.0407) in predicting the nonresponders. Conclusion: GLCM-based texture parameters extracted using FDG PET/CT are reproducible and can be used to identify nonresponders in patients with LABC.
Does positron emission tomography-computed tomography influence response assessment in patients of advanced gallbladder cancer on chemotherapy?
Mudalsha Ravina, Sanjay Gambhir, Sushma Agarwal, Rajan Saxena, Ajit Mishra
Department of Nuclear Medicine, SGPGIMS, Lucknow, Uttar Pradesh, India
Aim: Almost 90% of gall bladder carcinoma (GBC) patients are detected in advanced stages and merit chemotherapy. Computed tomography scan is the standard modality for assessment of response. Since positron emission tomography-computed tomography (PET-CT) gives information on metabolic response, our aim was to evaluate the utility of PET-CT in addition to CT scan. Methods: Patients with locally advanced and/or metastatic GBC were treated with a combination of cisplatin 25 mg/m 2 and gemcitabine 1 g/m 2 day 1 and 8 repeated 3 weekly for a total of 3 cycles. Response assessment was done with contrast-enhanced CT as well as PET. Responders were continued on further 3-5 cycles of the same regime while nonresponders were treated with a second line regime. Response assessment was done with RECIST as well as PERCIST. The response was categorized in four categories according to RECIST (complete response [CR], partial response [PR], stable disease [SD], and progressive disease [PD]) and PERCIST criteria (complete metabolic response [CMR], partial metabolic response [PMR], SD, and progressive metabolic disease [PMD]). Up- or down-staging was computed for each category. Results: Thirty-one patients (24 females and 7 males) had a median age of 50 years. According to RECIST criteria, PR rate was 16% (n = 5), SD 68% (n = 21), and PD 16% (n = 5). CMR was noted in 16%, PMR 32%, and PMD in 52%. PET upstaged response in 51% and downstaged in 16% patients. Among partial responders (n = 5), there was downstaging in one (CMR) and upstaging in two patients (PMD). Among patients with SD (n = 16), there was downstaging in three (CMR) and upstaging in ten patients (PMD). Among patients with PD (n = 5), there was downstaging in one (CMR) and upstaging in four patients (PMD). Conclusions: PET upstaged response in 51% and downstaged in 16% patients. The study elaborates that the metabolic response criteria (PERCIST) might be considered more suitable for evaluation of therapeutic response assessment for patients on chemotherapy in GBC in comparison to anatomical response criteria (RECIST).
"Bone marrow involvement in Hodgkin's disease on fludeoxyglucose positron emission tomography" - Does it translate into poorer survival?
Kunal Shaha, Nilendu Purandare, Sneha Shah, Archi Agrawal, V. Rangarajan
Department of Nuclear Medicine and Molecular Imaging, Main Building Basement, Tata Memorial Hospital, Mumbai, Maharashtra, India
Introduction: Bone marrow involvement in Hodgkin's disease (HD) is a poor prognostic marker. The Lugano classification 2014 recommended that, if fludeoxyglucose positron emission tomography-computed tomography (FDG PET-CT) is done for staging HD, bone marrow biopsy (BMB) can be obviated. Objective: To study the different patterns of marrow uptake in staging PET and its correlation with progression free survival (PFS) and overall survival (OS). Materials and Methods: This was a retrospective study. Ninety-nine consecutive newly diagnosed patients of HD, who had undergone staging PET and BMB, were enrolled in the study. Pattern of marrow uptake on PET was reported as focal, heterogeneous patchy, uniform diffuse, and no uptake. Focal and heterogeneous patchy uptake was considered positive while uniform diffuse and no uptake were considered negative for marrow involvement. Kaplan-Meir survival analysis was used to calculate PFS and OS. Results: Median follow-up of patients was 53 months. PET was positive in 23 of 99 patients. Fifteen patients had focal marrow involvement and 8 had heterogeneous patchy marrow involvement. Total 15 patients had relapsed and 5 of them died during the study period. PFS for patients with positive marrow involvement was 46 months while for negative marrow involvement was 61 months which was statistically significant (P < 0.01) using the log-rank test in the Kaplan-Meir analysis. OS for patients with positive PET was 55 months and for negative PET was 65 months, which was statistically significant (P = 0.03). Nearly 47% (7/15) patients with focal marrow uptake relapsed while only 11% (8/76) patients with negative marrow relapsed during the follow-up. No patients with heterogeneous patchy marrow involvement relapsed. Conclusion Focal FDG uptake was more indicative of marrow involvement as compared to diffuse FDG uptake. Patients with focal marrow uptake showed poor PFS and OS compared to patients with diffuse low-grade marrow uptake or marrow-negative patients.
"SIOPEN and modified Curie scores in Stage IV neuroblastomas" - Can these be validated using 18 F-fludeoxyglucose positron emission tomography/computed tomography?
Chaitali Bongulwar, Sneha Shah, Nilendu Purandare, Archi Agrawal, V. Rangarajan
Department of Nuclear Medicine and Molecular Imaging, Tata Memorial Hospital, Mumbai, Maharashtra, India
Objective: Radio-iodinated metaiodobenzylguanidine (mIBG) is an established imaging modality in neuroblastoma. Semiquantitative scoring-SIOPEN (International Society of Pediatric Oncology Europe Neuroblastoma Group) and modified Curie using radiolabeled mIBG are used for prognostication in high-risk neuroblastomas. The present study aims to use 18 F-fluorodeoxyglucose (FDG) for semiquantitative scoring and compares it with mIBG scores, thereby validating it for risk stratification. Methods: Data of 87 patients of high-risk neuroblastoma were retrospectively analyzed. mIBG scans were assessed according to the SIOPEN and the modified Curie scoring method. Similarly, 18 F-FDG PET/CT scans were also scored using these semiquantitative systems. The paired scans were compared at initial staging and end of induction therapy. A Curie score of 2 and a SIOPEN score 4 (best cutoff) described in previous studies were used to classify these scans into low- and high-risk and subsequently correlated with the clinical course of the disease. Results: At initial staging, there was a statistically significant difference between the Curie-FDG scores of 10.94 ± 10.0 as compared to mIBG score of 7.99 ± 9.00 with an increase of 2.94 with P = 0.001. In addition, there was a statistically significant difference between SIOPEN-FDG scores of 20 ± 26 as compared to mIBG (11.72 ± 20.00) with a difference of 8.27 and P = 0.12. At the end of induction therapy, there was no statistically significant difference (P > 0.01) between the Curie FDG and mIBG scores. Using the cutoff values for Curie and SIOPEN scores, 18 patients show discordance, of which 6 patients (33%) showed disease progression or death. Conclusion: Modified CURIE and SIOPEN score using 18 F-FDG shows an incremental value over mIBG score and can be correlated with the disease burden. The modified CURIE and SIOPEN score can be validated using 18 F-FDG PET/CT establishing their role in risk stratification.
| PET-CT or SPECT-CT|| |
Development and validation of suprathreshold stochastic resonance-based image processing method for detection of abdominopelvic tumor on positron emission tomography/computed tomography scans
Kartik Saroha, Anil Kumar Pandey, C. D. Patel, C. S. Bal and Rakesh Kumar
Nuclear Medicine Department, All India Institute of Medical Scuiences, New Delhi, India
Objective: The detection of abdominopelvic tumors embedded in or nearby radioactive urine containing 18 F-FDG activity is a challenging task on positron emission tomography/computed tomography (PET/CT) scan. In this study, we propose and validate suprathreshold stochastic resonance-based image processing method for detection of these tumors. Methods: The method includes addition of noise to the input image, and then thresholding it to create one frame of intermediate image. One-hundred such frames were generated and averaged to get the final image. The method was implemented using MATLAB R2013b on a personal computer. In this study, noisy image was generated using random Poisson variates corresponding to each pixel of the input image. To verify the method, 30 sets of pre- and its corresponding post-diuretic PET/CT scan images (25 tumor images and 5 control images with no tumor) were included. For each set of prediuretic image (input image), 26 images (at threshold values equal to mean counts multiplied by a constant factor ranging from 0.1-2.6 with increment step of 0.1) were created and visually inspected, and the image that most closely matched with gold standard (its corresponding postdiuretic image) was selected as the final output image. These images were further evaluated by two nuclear medicine physicians. Results: The empirical probability of detection of abdominopelvic tumors was found to be 0.88 (22 of 25 tumor images). In five control images, no false positives were reported. Conclusion: The proposed method was able to detect abdominopelvic tumors on prediuretic PET/CT scan with high probability of success and no false positives.
Evolving role of contrast-enhanced (F-18) fludeoxyglucose positron emission tomography-computed tomography in pyrexia of unknown origin in solid organ transplant recipients: Our initial experience
Avani S. Jain, M. Indirani, Shilpa Kalal, Jaykanth Amalachandran, S. Thangalakshmi, S. Shelley
Department of Nuclear Medicine, Apollo Main Hospital, Chennai, Tamil Nadu, India
Objective: fever in solid organ transplant (SOT) recipients presents one of the most challenging diagnostic situations. Opportunistic infections in an immunocompromised health state and graft rejections compounded by drug toxicities result in complex presentations. The aim of the study was to assess the role of contrast-enhanced F-18 fludeoxyglucose positron emission tomography-computed tomography (PETceCT) as a diagnostic tool in SOT recipients with pyrexia of unknown origin (PUO). Methods: A total of 39 adult patients (31 male, 8 female, and age ranging from 23 to 67 years) with SOT (30 renal transplants, 7 hepatic transplants, 1 cardiac transplant, 1 pancreas transplant) underwent whole-body (head to toe) PETceCT scan following a standard protocol on Philips GEMINI TF PET-CT scanner for evaluation of PUO during the years 2010-2016. The source of infection suggested by PETceCT was confirmed by biopsy and or follow-up up to 6 months. Results: PETceCT helped in localization of infective focus in 28/39 patients (infectious disease - 22, noninfectious inflammatory disease - 5, malignancy - 1). PUO resolved with no diagnoses and no evidence of disease in 8/39 patients. Tuberculosis (TB) was the most common infection found in SOT recipients. In a pancreas transplant recipient, possibility of lymphoma was suggested, which was confirmed to be TB on histopathology. Similarly, an imaging diagnosis of TB lymphadenitis in a renal transplant recipient was confirmed as adenocarcinoma on biopsy. PETceCT was unable to detect infective focus in a renal transplant recipient, who later developed cryptococcal meningitis. PETceCT studies were clinically helpful and contributory to diagnoses (71.79% positive contributory value and 20.51% contributory to exclusion of diagnosis). PETceCT had a sensitivity of 96.55%, specificity of 80%, positive predictive value of 93.33%, and negative predictive value of 88.89%. Conclusion: PETceCT is helpful in the diagnosis of PUO in SOT recipients and thus guides in the management of patients.
Development and verification of a computer program that reconstructs image from multiple parallel projections using filtered back-projection technique
Anil Kumar Pandey, Umesh Yadav, Kartik Saroha, C. D. Patel, C. S. Bal, Rakesh Kumar
Nuclear Medicine Department, All India Institute of Medical Scuiences, New Delhi, India
Objective: The aim of the study was to develop and verify a computer program that reconstructs image from multiple parallel projections using filtered back-projection technique. Methods: Computer program was implemented on personnel computer using MATLAB R2013b. To verify the program, projections from various angle of a known object (Shepp-Logan phantom, a widely used synthetic image designed to simulate the absorption of major areas of the brain, including small tumors) was obtained using radon transform. The filtered back-projected image was obtained as follows: (1) computing the one-dimensional (1D) Fourier transform of each projection; (2) multiplying each Fourier transform by the filter function (e.g., ramp filter, hamming filter, Hann filter, and Butterworth filter); (3) obtaining the inverse 1D Fourier transform of each resulting filtered transform; and (4) integrating all the 1D inverse transforms from Step 3 the program was also verified by real projection data obtained with single-photon emission computed tomography gamma cameras (Siemens NM and GE Healthcare). An interface function was written to read the projection data from DICOM files. The filtered back-projected image was obtained following the method as mentioned before. The reconstructed image from our developed program was compared with the image reconstructed by the vendor's software. Results: The computer program accurately reconstructed the phantom and patients image. However, the image quality of the reconstructed image with our program is not as sharp as the image quality of reconstructed image with vendor's software. Conclusion: The developed computer program accurately reconstructs the image from projection data using filtered back-projection technique.
Clinical utility of 99m Tc-ubiquicidin (29-41) in assessing musculoskeletal infection with a specific emphasis on prosthesis evaluation
Archana Mukherjee, Ajit Shinto 1 , Kamaleshwaran KK 1 , Jephy J 1 , Jyotsna Bhatt, Aruna Korde, Chanda Arjun 2 , Indira Upadhya 1 , Ashutosh Dash
Radiopharmaceuticals Division, Bhabha Atomic Research Centre, 1 Kovai Medical Center and Hospital Limited, Coimbatore, Tamil Nadu, 2 Quality Control-Radiopharmaceuticals, Board of Radiation and Isotope Technology, Navi Mumbai, Maharashtra, India
Objective: The purpose of this study was to evaluate utility of 99m Tc-ubiquicidin (UBI) (29-41) prepared from an indigenous cold kit in patients with suspected musculoskeletal infection. Method: Two cold kits vial of UBI (29-41) was prepared and utilized for preparation of patient dose of 99m Tc-UBI (29-41). Twenty-two patients, with suspected bone, soft tissue, or prosthesis infections, were included in the study. 370-555 MBq of 99m Tc-UBI (29-41) was injected intravenously in all the patients. A blood pool image at 20 min postinjection was followed by spot views of the suspected region of infection (target) and a corresponding normal area (nontarget) at 60 min. All patients underwent routine 99m Tc-methylene diphosphonate (MDP) 3-phase whole-body bone scan, followed by single-photon emission computed tomography-computed tomography (CT) of the prosthesis within a week of 99m Tc-UBI (29-41) study. Scans were interpreted on the basis of bacterial culture as the major criterion and the results of clinical tests, radiography, 18 F-fludeoxyglucose positron emission tomography-CT, and three-phase bone scanning as minor criteria. Results: Twenty-two studies were performed with 99m Tc-UBI (29-41). Sixteen scans showed positive and 6 showed negative for infection foci. Negative scans were subsequently confirmed to be true negative. Adverse reactions were not observed during image acquisition and within 5 days after the study. The overall sensitivity, specificity, positive, and negative predictive values were 100%, 85.7%, 93.75%, and 100%, respectively. A combination of MDP bone scan and UBI scans was considered to give maximum confidence toward reporting for the presence of infection. Conclusion : Patient dose of 99m Tc-UBI (29-41) was successfully prepared and simple quality control method to check radiolabeling yield was demonstrated at hospital radiopharmacy. 99m Tc-UBI (29-41) showed promise in localizing foci of infection, with optimal visualization at 20-60 min, especially for the evaluation of prosthesis loosening.
To correlate lymphoscintigraphy staging with clinical finding in lower limb lymphedema
Meetashree Nayak, M. Indirani, A. Jayakanth, S. Shelley
Department of Nuclear Medicine, Apollo Hospital, Chennai, Tamil Nadu, India
Aim: The aim of this study was to find out relationship between RNL image-based classification with clinical staging in lower limb lymphedema. Materials and Methods: Fifty patients between ages 20-70 years with clinically lower limb lymphedema without having venous disease were included in the study group. Radiolabeled nanocolloid (0.5-0.8 mCi in 0.2-0.4 ml) was injected intradermally into the first web space of both feet. Immediately after the injection, dynamic images were acquired for 2 min, postexercise image after 10 min, and delayed image after 3 h. Parameters were assessed: (a) clinical staging - Stage I - reversible, Stage II - irreversible, and Stage III - nonpitting edema/elephentasis. (b) Scintigraphy staging - Stage I - multiple channels or delay to flow, Stage II - Stage I with deep (popliteal) lymph nodes, Stage III - Stage II with dermal back flow, and Stage IV - no flow through lymphatics and nonvisualization of nodes. Results: In scintigraphic staging, 18 patients (36%) had one staging higher and 2 (4%) had one staging lower, when compared with clinical classification. In clinical classification, 21 patients (42%) had Stage I, 34% had Stage II, and 24% had Stage III. Of 21 patients who had Stage I in clinical classification, scintigraphically, 6 had Stage II. Similarly, 4 patients in Stage II and 8 patients in Stage III based on clinical classification had one stage higher in scintigraphy. Only two patients of 50, Stage III in clinical classification, is downgraded to Stage II in scintigraphy. Conclusion: Lymposcintigraphic staging provides functional status of lymphatics that is involved in disease process. Hence, it can be used as an additional tool in the armamentarium for patient management with lymphedema.
Feasibility of 99m Tc-MDM brain single-photon emission computed tomography semiquantitative index in radiotherapy treatment planning and follow-up response assessment and its correlation with histopathology of glioma
Nisha Rani, Baljinder Singh, Narendra Kumar, Puja P. Hazari, Paramjeet Singh, Anish Bhattacharya, Ambika Parmar, Anil K. Mishra
Department of Nuclear Medicine, Nehru Hospital, PGIMER, Chandigarh, India
Objective: To evaluate the feasibility of 99m Tc-MDM brain single-photon emission computed tomography (SPECT) semiquantitative index in radiotherapy treatment (RT) planning/assessment and correlation with histopathology in patients with glioma. Methodology: Thirty patients with histologically proved glioma have been included: 19 - glioblastoma multiforme-G-IV, 3 - anaplastic oligodendroglioma/oligoastrocytoma-G-III, 6 - astrocytoma/oligodendroglioma-G-II, and 2 - pilocytic astrocytoma-G-I. A total of 45 MDM-SPECT scans were performed and assessed by 99m Tc-MDM brain SPECT-computed tomography (CT) and magnetic resonance imaging (MRI) at (a) the of planning of RT and chemotherapy and (b) after the completion of RT to evaluate the radiotherapy response. Final response was evaluated by comparing SPECT-CT and MRI results. The uptake of MDM in tumor was measured as tumor:background ratio (TBR) and was generated to assess irradiation effect on tumor. Paired t-test was used for comparison of pre- and post-radiotherapy TBR, and independent t-test was used for assessing the grade of malignancy correlation with TBR semiquantitative index. Results: The present study used 99m Tc-MDM kits preparations with mean radio labeling efficiency of 97.0% ± 1.5% (n = 45). In quantitative evaluations, patients with low TBR ratio initially had significantly better prognosis. MDM exhibited a slightly higher TBR ratio in high-grade glioma (n = 19; mean TBR = 3.38 + 1.71) than in low-grade gliomas (n = 8: mean TBR = 1.95 + 0.74), and difference of tumor-to-contralateral brain uptake ratios of MDM between Grades IV/III and Grades II/I gliomas was statistically significant (P < 0.03). Fifteen patients were studied at 4 months' post-RT and 99m Tc-MDM brain SPECT was compared and TBR ratios was significantly (P < 0.04) different at pre- and post-RT. Conclusions: As Methionine uptake by normal brain is relatively low, MDM-SPECT may show promise in assessment of cerebral tumor dimensions. Radiotherapy is one of the primary treatments of Gliomas. 99m Tc-MDM brain SPECT-CT can play various roles.
Role of 18 F-fludeoxyglucose positron emission tomography/computed tomography in symptomatic postrenal transplant patients
Abhishek Behera, S. T. Arun Raj, Krishna Kant Agarwal, Sameer Taywade, Rakesh Kumar, C. S. Bal
Department of Nuclear Medicine, All India Institute of Medical Sciences, New Delhi, India
Objective: The aim of this study was to evaluate the utility of 18 F-fludeoxyglucose positron emission tomography/computed tomography ( 18 F-FDG PET/CT) in the diagnosis and evaluation of symptomatic postrenal transplant patients. Postrenal transplant patients are a distinct subset of patients with very different diagnostic needs. Due to prolonged immunosuppression required for renal transplantation, there exist very distinct disease processes not usually seen in immune competent patients. The aim of this retrospective analysis was to analyze the diagnostic contribution of 18F-FDG-PET/CT in the diagnosis of symptomatic renal transplant recipients. Methods: Patients were retrospectively recruited from a patient study database with a recruitment cutoff date of August 31, 2016. The 18 F-FDG-PET/CT scanning had been done 60 min after intravenous injection of 10 mCi of 18 F-FDG. Scan findings were analyzed and compared with either final histopathological diagnosis or using clinical follow-up data and in one case using a follow-up 18 F-FDG PET/CT. Fourteen patients were included in this analysis. Results: The most common presenting were chronic diarrhea and weight loss (8 patients), fever of unknown cause (3 patients), graft dysfunction (3 patients), and multifocal lymphadenopathy with refractory anemia and accelerated hypertension in one patient. Of the 14 patients, 18 F-FDG PET/CT was able to aid diagnosis in 9 patients (sensitivity of 64%). Of the 9 patients, 6 patients were found to have posttransplant lymphoproliferative disease (5 patients of immunoproliferative small intestinal disease [IPSID] and one patient with peri-graft lymphoproliferative lesion). One patient was found to have pancreatitis. One patient was found to have evidence of active Pneumocystis pneumonia in the lungs, along with lymphoma. Two patients were found to have fungal lung infections (including one patient diagnosed to have IPSID). Conclusion: 18 F-FDG PET/CT has a potential utility in the evaluation of symptomatic postrenal transplant patients with the ability to search for, and evaluate activity of various disease processes specific to renal transplant patients.
| Award Paper: Hepatology|| |
Threshold method for volume and activity determinations using single-photon emission computed tomography phantom for possible use in clinical liver therapies
Amritjyot Kaur, Virendra Singh 1 , Anish Bhattacharya, Ratti Ram Sharma 2 , Ajay Chitkara, Shalini Chopra, Baljinder Singh
Departments of Nuclear Medicine, 1 Hepatology and 2 Transfusion Medicine, PGIMER Chandigarh, India
Objective: A threshold method for volume and activity determinations was developed through the use of a series of single-photon emission computed tomography (SPECT) phantom studies. The estimated threshold values were used to calculate the liver volume (LV) and radioactivity measurements on 99m Tc-S colloid SPECT/CT images in patients with cirrhosis. Materials and Methods: Series of phantom measurements were performed using volumes of 6-3200 ml and varying concentrations between 0.4 and 10.27 µCi/mL acquired on dual-headed gamma camera (Symbia T16, SIEMENS, Germany); 120 projections (20 s/projections); 128 × 128 matrix; zoom 1. Images were reconstructed by filtered backprojection using Butterworth filter (cutoff 0.5 cycles/cm). 99m Tc-S colloid SPECT/CT scan with standardized parameters was performed on cirrhotic patients (n = 11). LV, spleen volume (SV), quantitative liver uptake (QLU), quantitative spleen uptake (QSU), % injected dose/mL (%ID/mL) liver, and % injected dose/mL (%ID/mL) spleen were calculated. Results: Threshold was calculated using three-dimensional volumetric analysis 126.96.36.199 software. The best threshold value for both attenuation and nonattenuation corrected images for 6-3800 mL is 38 and 37 (r = 0.978; 0.989). For concentration from 0.4 to 10.27 µCi/mL, the regression line equation obtained for concentration on attenuation corrected and nonattenuation corrected images is counts/cc = 3829 × µCi/cc + 3790 (r = 0.97) and counts/cc = 2533 × µCi/cc + 268 (r = 0.99), respectively. For patients of Child Pugh score Class A (n = 6) and Class C (n = 5), LV (1469 ± 247; 630 ± 62), SV (545 ± 34; 479 ± 19), QLU (41.72 ± 14.48; 10.34 ± 1.25), QSU (51.53 ± 17.62; 58.23 ± 2.64), %ID/mL liver (0.0287 ± 0.008; 0.017 ± 0.0006) %ID/mL spleen (0.05 ± 0.02; 0.107 ± 0.012) were obtained. Conclusion: The best threshold value for both attenuation and nonattenuation corrected data was found to be 38%. SPECT quantitation may be a useful tool for assessment of severity of liver disease and its quantification after liver therapies.
Hepatic cirrhosis versus noncirrhotic portal hypertension as cause of portal hypertension - Usefulness of Tc-99m sulfur colloid scan
Madhur Kumar Srivastava, P. Manohar, S. Vinod, N. Kavitha, Ajit Kumar
Department of Nuclear Medicine, Nizam's Institute of Medical Sciences, Punjagutta, Hyderabad, Telungana, India
Introduction: Cirrhosis and noncirrhotic portal hypertension (NCPH) are important causes for portal hypertension (PTH). The management of the disease changes according to the etiology. The definite diagnosis is by liver biopsy, which is an invasive procedure. This study was performed to assess usefulness of Tc-99m sulfur colloid scan (SC scan), a noninvasive test, in differentiating hepatic and extra-hepatic causes of PTH. Materials and Methods: This is a retrospective analysis of 221 patients with SC scan in the past 3 years with symptoms pertaining to PTH. Of these, 5 patients had undergone prior splenectomy, and hence were excluded from the final analysis. The scan was performed by usual protocol. The analysis was performed in terms of liver size, spleen size, liver to spleen uptake (L:S) ratio, and marrow uptake. Results: The final analysis of 216 patients showed cirrhosis in 88, NCPH in 118, and normal scan in 10 patients. Shrunken liver was noted in 32 patients. Hepatomegaly was seen in 28 patients, of which 11 (39%) showed colloid shift. Forty-five patients had normal liver size with left lobe hypertrophy with colloid shift suggesting early hepatic cirrhosis. Splenomegaly was observed in 190 patients (87.9%). Of 88 patients, 75 (85%) cirrhotic patients showed L:S ratio <1, suggesting hepatic dysfunction, while rest 13/88 (15%) showed L:S ratio >1 with marrow uptake. All patients with NCPH showed L:S ratio >1. Bone Marrow uptake was noted in 44 patients, all having cirrhotic liver, but was normal in rest 44 cirrhotic patients. All NCPH patients showed undetectable marrow uptake. The sensitivity and specificity of L:S ratio for detection of hepatic cause of portal HTN was 85.2% and 100%, respectively, while that of marrow uptake was 50% and 100%, respectively. Conclusion: Tc-99m SC scan is an important noninvasive test to differentiate between hepatic and extrahepatic causes of PTH, and liver to spleen ratio is most sensitive parameter.
Can transarterially injected Tc-99m macroaggregated albumin predict pulmonary chemotoxicity in transarterial chemoembolization patients?
P. A. Meivel, P. Madhusudhanan, Biju Pottakat, Anand Shankar, M. S. Bharadwaj, Nandini Pandit, H. Dhanapathi
Department of Nuclear Medicine, JIPMER, Puducherry, India
Background and Aim: Patients undergoing transarterial chemoembolization (TACE) are subject to the risk of pulmonary chemotoxicity due to shunting of blood. To study the feasibility of identifying pulmonary shunt in patients undergoing TACE. Materials and Methods: Patients who were diagnosed with nonmetastatic hepatocellular carcinoma underwent selective arterial catheterization through femoral route for TACE. Prior to injection of chemotherapeutic agent, freshly prepared Tc-99m macroaggregated albumin (MAA) was injected into the arterial branch that supplied the tumor. After TACE procedure was complete, patients were shifted to nuclear medicine department for imaging. Static image of thorax and abdomen with liver and lungs in the field of view was acquired in anterior and posterior views on 256 × 256 matrix. Regions of interest were made around the lungs and the whole of field of view on a geometric mean image. The percentage of tracer reaching the lungs was calculated. Results: Two patients had undergone Tc-99m MAA injection during TACE. Both patients had hepatocellular carcinoma involving right lobe of liver. The percentage uptake in the lungs was calculated and was found to be 22% and 20% in the two patients. Conclusion: It is feasible to perform Tc-99m MAA perfusion scan during TACE to find out the percentage of pulmonary shunt. It may be helpful in predicting pulmonary toxicity in such patients.
Nonexcretory hepatobiliary scans in neonatal cholestasis and their outcome
M. S. Bharadwaj, P. Madhusudhanan, H. Dhanapathi, Nandini Pandit, S. Kumaravel, Barath Jagadisan
Department of Nuclear Medicine, JIPMER, Puducherry, India
Objective: To evaluate the outcome of nonexcretory report of hepatobiliary scintigraphy in cases of neonatal cholestasis. Methods: A retrospective analysis of hepatobiliary scan reports pertaining to the period February 2010 to June 2016 was performed. Scans which did not show any excretion even on 24-h images were selected. All patients had undergone the scan after being primed with 3-5 days of ursodeoxycholic acid or 5 days of phenobarbitone. Scans were done with 1-2 mCi of Tc-99m mebrofenin and multiple static images of abdomen and pelvis were acquired up to 24 h. Age, gender, biochemical parameters, biopsy findings, and operative procedures performed were noted down. Findings of liver biopsy or per operative cholangiogram were considered as confirmatory test for biliary atresia. Results: A total of 99 children had nonexcretory hepatobiliary scan results during the study period. The median age of the children was 60 days (IQ 30-60) and the male:female ratio was 1.25:1. Confirmatory tests in the form of biopsy or peroperative cholangiogram were available for 79 of these patients. Fifty of the children (63%) were finally categorized as biliary atresia based on biopsy/per-operative findings. The remaining had neonatal hepatitis (n = 24). One each of the children had Alagille syndrome, alpha 1 antitrypsin deficiency, Galactosemia, portal triaditis, and familial intrahepatic cholestasis Type III. Conclusion: Hepatobiliary scintigraphy is a useful tool for ruling out biliary atresia in patients with neonatal cholestasis. A significant proportion (63%) of the patients with nonexcretory scans finally turned out to have biliary atresia.
| Award Paper: Thyroidology|| |
Efficacy of radioactive iodine therapy in thyrotoxicosis patients: An experience of tertiary care hospital
Ashish Kamra, Preeti Singh, Shwetal Pawar, Mangla Ghorpade, Suruchi Shetye
Department of Nuclear Medicine, Seth G. S. Medical College and K. E. M. Hospital, Mumbai, Maharashtra, India
Objective: Radioactive iodine (I-131) (RAI) has been commonly used for the treatment of both benign thyroid conditions. Our aim of RAI therapy is to assess response of RAI in thyrotoxicosis to render the patients either euthyroid or hypothyroid. Methods: Sixty-four (49 females, 15 males) thyrotoxic patients were categorized into Grave's disease, toxic multinodular goiter (MNG), and autonomous functioning thyroid nodule (AFTN). These patients were given 10 mCi in Grave's disease and 15 mCi in AFTN and MNG of RAI. Six Grave's disease patients were treated twice with RAI. Patients were on a variable period of dose and duration of neomercazole. Four patients were referred for RAI therapy due to toxicity to drugs. These patients were followed for a mean period of 8 months. Response evaluation was done at 6 months in terms of T3, T4, and thyroid-stimulating hormone. These patients were subcategorized into euthyroid, hypothyroid, and hyperthyroid. Euthyroid and hypothyroid status was considered treatment success and hyperthyroid status as treatment failure. Results: Out of 47 Grave's disease patients, in 76.6% (36) of patients, treatment was successful and the rest 23.4% (11) showed failure of treatment. Out of 5 toxic MNG patients, in 60% (3) patients, treatment was successful and in 40% (2) treatment was failure. In 12 AFTN patients, there was 100% treatment response. There was no correlation found between the dose or duration of neomercazole on the efficacy of RAI. Conclusion: RAI therapy showed best results in the treatment for AFTN followed by Grave's disease and toxic MNG in rendering the patients euthyroid or hypothyroid.
Comparison of both lobes of thyroid following thyroidectomy in low-risk differentiated thyroid cancer
Department of Nuclear Medicine, Christian Medical College, Vellore, Tamil Nadu, India
Objective: In low-risk differentiated thyroid carcinoma (DTC), appropriate surgical procedure in terms of hemi/total thyroidectomy has been an area of debate. In background of this, studies have stated that a hemithyroidectomy is sufficient in these patients. This finding has also been recommended by the latest ATA 2015 guidelines that thyroid lobectomy alone may be sufficient in initial treatment for low-risk DTC. In background of this, our aim was to assess relevance of total thyroidectomy and compare histology of both lobes and also profile of follow-up in low-risk DTC patients. Methods: We retrospectively analyzed histopathological reports of 400 patients with DTC who underwent radioactive iodine following total/completion thyroidectomy in Christian Medical College from 2008 to 2014. Patients with low-risk features (primary tumor <4 cm in diameter, no extrathyroidal extension and no nodal metastases) were 100 and these were analyzed. Results: Out of 100 patients between 15 and 62 years (71 females and 29 males), 26 were tumor in both lobes, 18 - microcarcinomas in other lobe, and 56 - free of tumor in other lobe. Therefore, 44% of patients were found to have tumor in other lobe which implied that total thyroidectomy was beneficial as compared to hemithyroidectomy alone, in low-risk patients. Of these 100 patients, only 3 were subjected to repeat ablation. In follow-up, it was found that 13% had residual at 6 months of follow-up and 9% patients had persistent residual at 1-year follow-up and 4% continued to have residual uptake even after 3 years of follow-up. Conclusion: The role of total thyroidectomy in low-risk DTC patients as first line of treatment cannot be underestimated, as a significant number of patients were found to have tumor in contralateral lobe as well, which would have otherwise been overlooked if only lobectomy would have been strictly followed in these patients. As all these patients were subjected to radioiodine therapy, only 13% of these patients were found to have residual in 6-month follow-up.
99m Tc methoxy isobutyl isonitrile as predictor of malignancy in hypofunctioning thyroid nodules
M. S. Bharadwaj, Madhur Kumar Srivastava, P. Madhusudhanan, H. Dhanapathi, Nandini Pandit, Surendra Kumar Verma
Department of Nuclear Medicine, JIPMER, Puducherry, India
Objective: There is a renewed interest in the use of Tc-99m methoxy isobutyl isonitrile (MIBI) to assess likelihood of malignancy in thyroid nodules, particularly in those with indeterminate cytology. This study was aimed to analyze the ability of Tc-99m MIBI in differentiating benign from malignant nodules in comparison with fine-needle aspiration cytology (FNAC). Methods: Patients who had hypofunctioning nodule on thyroid scintigraphy performed between 2013 and 2015 underwent additional scan with 15-20 mCi of 99m Tc MIBI on a different day. Planar images were acquired at 15 and 90 min. MIBI scans were categorized into three groups: Group A (no uptake), Group B (same uptake as thyroid), and Group C (more uptake than thyroid) based on 15 min images. MIBI scan findings were compared with FNAC reports. Results: A total of 45 patients were included in the study. A number of patients in various groups were as follows: Group A = 13, Group B = 4, and Group C = 28. FNAC reports were as follows: Bethesda category II - 34, III - 1, IV - 3, V - 2, and VI - 5. FNAC reports as per groups were Group A (II - 11, IV - 1, and V - 1), Group B (II - 3 and IV - 3), and Group C (II - 20, III - 1, IV - 1, V - 1, and VI - 5). Whereas patients in Group B had either benign (n = 3) or follicular neoplasm (n = 1), patients in Group A had predominantly either benign (n = 11) or follicular neoplasm (n = 1). One patient in Group A had Bethesda V. The largest number (21%) of Bethesda IV and V were seen in Group C patients (n = 1 and n = 5, respectively). On analysis of delayed MIBI images, many benign lesions (Bethesda II) were found to show washout (71% of all lesions that showed washout pattern) and many others showed retention (76% of lesions that showed retention). No significant difference was found between washout/retention pattern of benign lesions (P = 0.75). Conclusion: Although all malignant lesions in our series had good MIBI uptake in the early images, many benign lesions showed uptake as well as significant retention. Visual interpretation of MIBI washout alone cannot be relied upon to assess likelihood of malignancy.
Scintigraphic presentations of ectopic thyroid gland
P. A. Meivel, Dhanapathi Halanaik, Nandini Pandit, Madhusudhanan Ponnusamy, Sreenivasa Reddy, Sarath Kumar, Naveen Kumar Reddy
Department of Nuclear Medicine, JIPMER, Puducherry, India
Introduction: Ectopic thyroid along with thyroglossal cyst accounts for the majority of developmental thyroid abnormalities. Ectopic thyroid is commonly detected when patient presents with clinical features such as neck swelling or symptoms of hypothyroidism. The detection of ectopic thyroid can be made with imaging modalities such as ultrasound, computed tomography, magnetic resonance imaging, and nuclear imaging. Aim: To study patient characteristics and location of ectopic thyroid gland in patients referred for thyroid scintigraphy. Materials and Methods: Retrospective review of thyroid scans performed between February 2010 and August 2016 was done. Scans that showed ectopic thyroid tissue were selected. Patient characteristics such as age, gender, presenting features, serum thyroid-stimulating hormone values, and thyroid scintigraphy findings were noted down. We classified ectopic thyroid into three main types based on their location as lingual, region of hyoid, and lateral or inferior part of neck. Results: A total of 42 scans were found to have functioning ectopic thyroid tissue. The median age of the patients was 10 years (IQ range - 7-23 years) and the number of males and females were 10 and 32, respectively. The clinical presentations were swelling in neck, developmental delay, clinical diagnosis of congenital hypothyroidism, foreign body sensation in throat, and dysphagia. TSH values were available for 37 patients (euthyroid-13, hypothyroid-23 and hyperthyroid-1). Out of 45 ectopic thyroid foci found on scintigraphy, 23 were in lingual region, 18 in hyoid region, and 4 in the lateral aspect or inferior part of neck. Three patients had dual ectopic thyroid and three had ectopic thyroid in the presence of eutopic thyroid gland. Conclusion: In our series, a majority of the patients presented with neck swelling. Lingual region was the most common location of ectopic thyroid. Thyroid scintigraphy is an effective and sensitive imaging modality to detect and locate functioning of ectopic thyroid.
Comparison of conventional ultrasound, color Doppler, power Doppler, elastography, and contrast-enhanced ultrasonography parameters with histopathology findings in the differential diagnosis of nodules
Sanjana Ballal, Madhav P. Yadav, Arun K. Gupta 1 , Manisha Jana 1 , Suryanarayana S. V. Deo 2 , Chandrasekhar Bal
Departments of Nuclear Medicine, 1 Radiology and 2 Surgical Oncology, All India Institute of Medical Sciences, New Delhi, India
Background: Although neck ultrasound is the first line of choice for the screening of thyroid nodules, a very few studies have compared the diagnostic performances of both conventional and advanced ultrasound parameters. In this study, we aim to compare various conventional and advanced ultrasound imaging parameters and confirm it with histopathology findings to differentiate between benign and malignant thyroid nodules. Methods: One-hundred and thirty nine patients with 173 thyroid nodules underwent conventional ultrasonography (cUSG) which included gray-scale parameters, color Doppler, and power Doppler (PD) followed by elastography and contrast-enhanced ultrasonography (CEUSG). Post-USG imaging, all patients underwent fine-needle aspiration cytology followed by surgery if indicated and histopathological results were obtained. Stata 11.2 statistical software was used for the statistical analysis. Results: Of 173 nodules, 65 were benign and 108 were malignant. cUSG had a sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), and accuracy of 94.4%, 90.4%, 94.4%, 90.4%, and 91.9%, respectively, with area under the curve [AUC]: 0.97. On ROC analysis, the cutoff value for differentiating malignant from benign thyroid nodules on Ueno elasticity scoring was >3; AUC: 0.86 versus >2.2 using elasticity ratio method, AUC: 0.90. CEUSG and elastography had sensitivity, specificity, PPV, NPV, and accuracy of 93.8%, 95.3%, 97.2%, 89.8%, and 94.2%, respectively, with AUC: 0.98. On combining and ranking both conventional and advanced cUSG parameters, the significant indicators for malignancy were heterogeneous contrast enhancement, followed by Type-IV/V PD flow patterns, absence of ring enhancement, and elasticity ratio >2.2 patterns with the largest AUC: 0.994. Conclusions: Conjoint analysis of specific features of thyroid nodules on cUSG, elastography, and CEUSG will enhance the diagnostic value in the screening of thyroid nodules.
Diagnostic utility of 99m Tc methoxy isobutyl isonitrile for detecting residual gland, local, and distant metastases in postoperative patients with differentiated thyroid carcinoma
K. B. Sarath, H. Dhanapathi, K. S. Sunil, P. Nandini, P. Madhusudhanan
Department of Nuclear Medicine, SSB, JIPMER, Puducherry, India
Objective: To assess the diagnostic value of 99m Tc-methoxy isobutyl isonitrile scan (MBS) and compare with 131 I diagnostic whole-body scan (WBS) for identifying residual gland, local, and distant metastases among postoperative patients with differentiated thyroid cancer (DTC). Methods: Fifty-two patients (45 females, 7 males; 19-68 years, mean −36.40 +11.79) referred for radioiodine therapy were included in the study. With proper informed consent, MBS and WBS were performed after thyroxine withdrawal (mean thyrotropin-116.90). They received I-131 therapy according to stage and risk stratification (median of I-131 dose-30 mCi; IQ range: 30.0-144.5). Posttherapy whole-body scan (PTS) was done after 3-10 days. Scan profiles of MBS were compared with WBS and PTS. The accuracy of MBS was expressed as sensitivity, specificity, and predictive values with PTS as gold standard. The degree of agreement with WBS and PTS was expressed with kappa statistics. Results: Forty-seven patients had papillary thyroid carcinoma and its variants (90.4%) and 4 patients had follicular thyroid carcinoma (7.7%). One case (1.9%) had both follicular carcinoma and Papillary microcarcinoma. The sensitivity values of MBS for detection of residual thyroid gland, lymph nodal metastases, and distant metastases are 28.6%, 22.2%, and 40%, respectively. The specificities and positive predictive values are 100% for all the three entities. Negative predictive values are 7.89%, 86.0%, 94.0% in the same order. The degree of agreement between MBS and PTS is 4.4% (P - 0.279), 32.1% (0.002), and 54.7% (0.00) for detection of residual thyroid gland, lymph nodal metastases, and distant metastases, respectively. The degree of agreement between MBS and WBS is 4.4% (P - 0.279), 17.3% (0.123), and 29.7% (0.02) for detection of residual thyroid gland, lymph nodal metastases, and distant metastases, respectively. Conclusion: Due to low sensitivity, MBS may not replace WBS for the initial evaluation of DTC patients before radioiodine therapy. It may be used as a diagnostic tool to detect metastasis without having to withdraw thyroxine in follow-up.
Method of 131 I-thyroid uptake calculation using gamma camera system
Prathamesh R. Rajai, Madhuri S. Shimpi, Amit Abhyankar, Natasha Singh, Akshay Bedmutha, Melvika Parera, Suvidha Posam
Department of Nuclear Medicine, P. D. Hinduja National Hospital and MRC, Mumbai, Maharashtra, India
Objectives: Dosimetry method is one of the methods used to decide radioiodine dose for Treatment of hyperthyroidism. Two approaches are generally used to calculate radioiodine uptake by gamma camera with and without subtraction of background counts. We evaluated the difference in determining thyroid uptake caused by these two methods of calculation. Methods: Fifty patients with hyperthyroidism referred for radioiodine treatment to our hospital were included in this study. We calculated radioiodine uptake at 2 and 24 h by the method with background counts subtraction (method 1: corrected neck counts/standard × 100; corrected neck counts: neck counts − background counts [neck pixel area/background pixel area]) and other one is nonbackground counts subtraction (method 2: neck counts/standard × 100). Values were analyzed by Wilcoxon signed-rank test as these data are nonparametric nonnormal distribution data. Results: We found statistically significant difference between uptake values of two methods (P < 0/001) with median value at 2 h by method (1) was 17.7% (minimum 2.21% and maximum 68.7%) and by method (2) was 28.25% (minimum 5.79% and maximum 86.84). Uptake median value at 24 h by method (1) was 47.53 (minimum 4.08 and maximum 81.02) and by method (2) was 68.80 (minimum 7.73, maximum 97.32). Conclusions: Although the nonbackground correction is simple and convenient for calculation, it gives overestimated neck uptake. As in dosimetry method, the neck uptake value is an important factor so we conclude that background correction neck counts should take into consideration while calculating the uptake values.
Correlation between BRAF-V600E mutations and clinicopathologic parameters in papillary thyroid cancer: a study in Indian population
Sanjana Ballal, Sunil Shakya, Madhav Prasad Yadav, Sandeep Mathur, Suryanarayana V. S. Deo, Chandrasekhar Bal
Department of Nuclear Medicine, Thyroid Clinic, AIIMS, New Delhi, India
Objective: Papillary thyroid carcinoma accounts for 75%-80% of the carcinomas and the BRAF-V600E mutation is the most common genetic alteration in papillary thyroid cancer (PTC). In this study, we analyze the correlation between these alterations and clinicopathologic parameters in PTC in Indian population. Methods: In this retrospective study, 118 patients with papillary carcinoma were chosen and analyzed. In all patients, paraffin-embedded blocks were available for DNA extraction. DNA extraction was performed by the kit-based method followed by amplification by polymerase chain reaction and sequencing of exon 15. Results: BRAFV600E mutation was detected in 26/118 (23%) patients. The mutation pertained only to classic PCT. None of the other variants of PCT showed mutation in exon 15. BRAF-V600E mutation is associated with extra thyroidal extension, nodal metastases, first dose I-131 failure, disease progression, and persistent disease at final follow-up. BRAF-V600E mutation is significantly associated reduced disease-free survival and reduced event-free survival. Conclusion: The prevalence of BRAF-V600E mutation in India is 23%. The prevalence of mutation in Indian population is less than other parts of the world. BRAF-V600E mutation is a potential prognostic factor in PTC patients. Our study findings support further investigation of therapeutic implication of BRAF-V600E prevalence in PTC.
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