Rakhee Vatsa

Quality control of positron emission tomography radiopharmaceuticals: An institutional experience.

Purpose of the Study: To study quality control parameters of routinely prepared positron emission tomography (PET) radiopharmaceuticals. Materials and Methods: Three PET radiopharmaceuticals fluorine-18 fluorodeoxyglucose (F-18 FDG), N-13 ammonia (N-13 NH3), and Ga-68 DOTATATE (n = 25 each), prepared by standardized protocols were used. The radionuclide purity, radiochemical purity, residual solvents, pH, endotoxins, and sterility of these radiopharmaceuticals were determined. Results: The physical half-life of radionuclide in radiopharmaceuticals, determined by both graphical and formula method, demonstrated purity of radionuclides used. pH of all PET radiopharmaceuticals used was in the range of 5-6.5. No microbial growth was observed in radiopharmaceutical preparations. The residual solvents, chemical impurity, and pyrogens were within the permissible limits. Conclusions: All three PET radiopharmaceuticals were safe for intravenous administration.

Detailed evaluation of different 68Ge/68Ga generators: an attempt toward achieving efficient 68Ga radiopharmacy

The present study is aimed at carrying out a comparative performance evaluation of different types of (68)Ge/(68)Ga generators to identify the best choice for use in (68)Ga-radiopharmacy. Over the 1 year period of evaluation, the elution yields from the CeO2-based and SiO2-based (68)Ge/(68) Ga generators remained almost consistent, in contrast to the sharp decrease observed in the elution yields from TiO2 and SnO2-based generators. The level of (68)Ge impurity in (68)Ga eluates from the CeO2 and SiO2-based (68)Ge/(68)Ga generator was always <10(-3)%, while this level increased from 10(-3)% to 10(-1)% in case of TiO2 and SnO2-based generators. The level of chemical impurities in (68)Ga eluates from CeO2 and SiO2-based (68)Ge/(68)Ga generators was negligibly low (<0.1 ppm) in contrast to the significantly higher level (1-20 ppm) of such impurities in eluates from other two generators. As demonstrated by radiolabeling studies carried out using DOTA-coupled dimeric cyclic RGD peptide derivative (DOTA-RGD2), CeO2-PAN and SiO2-based generators are directly amenable for radiopharmaceutical preparation, whereas the other generators can be only used after post-elution purification of (68)Ga eluates. Clinically relevant dose of (68)Ga-DOTA-RGD2 was prepared in a hospital radiopharmacy for non-invasive visualization of tumors in breast cancer patients using positron emission tomography.

Integrin αvβ3 as a Promising Target to Image Neoangiogenesis Using In-House Generator-Produced Positron Emitter 68Ga-Labeled DOTA-Arginine-Glycine-Aspartic Acid (RGD) Ligand

For the growth and spread of a tumor beyond 2 mm, angiogenesis plays a crucial role, and association of various integrins with angiogenesis is evidential. The aim of the study was radiolabeling of DOTA-chelated RGD (arginine-glycine-aspartic acid) peptide with (68)Ga for PET imaging in locally advanced breast carcinoma. DOTA-RGD was incubated with (68)GaCl3, eluted in 0.05 m HCl. Elution volume, peptide amount, and reaction pH were studied. Radio-ITLC, gas chromatography, endotoxin, and sterility testing were performed. Serial (n=3) and whole-body (n=2) PET/CT imaging was done on patients post i.v. injection of 111-185 MBq of (68)Ga-DOTA-RGD. Maximum radiolabeling yield was achieved with 3 mL elution volume of 15-20 μg peptide at pH 3.5-4.0 with 10 minutes of incubation at 95°C. Product samples were sterile having 99.5% radiochemical purity with residual ethanol content and endotoxins in injectable limits. Intense radiotracer uptake was noticed in the tumor with SUVmax 15.3 at 45 minutes in serial images. Physiological radiotracer uptake was seen in the liver, spleen, ventricles, and thyroid with excretion through the kidneys. The authors concluded that (68)Ga-DOTA-RGD has the potential for imaging α,vβ3 integrin-expressing tumors.

Noninvasive treatment of keloid using customized Re‐188 skin patch

Keloids are developed as fibrotic scar at the site of surgery or trauma and often enlarge beyond the original scar margins. Re‐188 colloid coated customized patch was superficially fixed onto the lesion for 3 hrs. The same patch was reapplied on the lesion on third day for 3 hrs. The patients were followed up at 1, 3,6 and 12 months post treatment. The size and elevation of the keloid lesion was reduced after treatment. The total radiation dose from the patch (day‐1 and day‐3) was 100 Gy/mCi of Re‐188. The radioactive patch treatment of keloids is noninvasive, painless and safe with prolonged outcome.

Gel clot bacterial endotoxin test of FDG: Indian scenario

Background: The bacterial endotoxin test (BET) performed using gel clot method is a 60-min test and typically performed after the decay of the 2-(18F) fluoro-2-deoxy-d-glucose (F18-FDG) sample to determine the endotoxin content. The objective of this study protocol was to perform BET testing of F18-FDG by gel clot method. Materials and Methods: Ten random decayed samples of the F18-FDG were subjected to the gel clot BET. The assay was performed with undiluted F18-FDG and at four different maximum valid dilutions of 1:10, 1:100, 1:350 and 1:700 (total number of tests = 100). The sensitivity of the LAL reagent used was 0.125 EU/ml. Endotoxin dilutions were freshly prepared from control standard endotoxin (CSE) stock solution for each F18-FDG batch testing. If the gel had formed and remained intact in the bottom of the reaction tube after an inversion of 180°, the test was considered positive. Any other state of the reaction mixture constituted a negative test. Results: In the undiluted samples, the measured pH (7.05) was well within the acceptable range (i.e. 6.0–8.0) for the gel clot assay. Of the 10 undiluted F18-FDG batches and all the diluted samples, none gelled after 60-min incubation period at 37°C. However, the undiluted F18-FDG did inhibit gel formation at the lysate sensitivity of 0.125 EU/ml. Conclusion: The total volume of FDG produced was 16 ml in the synthesis module. The total F18-FDG preparation at any time did not contain more than 8 EU (0.5 EU/ml × 16 ml). Thus, the product is safe for human administration.

Multifarious Ga-68 labeled PET radiopharmaceuticals in imaging various malignancies

The gamut of gallium labeled radiopharmaceuticals contributes to augmented variety in molecular imaging approach for in vivo identification of tumor characteristics. The spectrum ranges from somatostatin receptor based target-specific imaging agents, to those used for tumor imaging based on specific receptor types extending into ones used for therapeutic monitoring. The versatility of gallium chemistry provides the needed advantage for imaging which is further exploited in clinical practice influences the specificity of tumor imaging. Ga-68 has revealed applicability in labeling compounds from nanoparticles to micro as well as macromolecules. We in this image, present variety of frequently and infrequently used gallium labeled radiopharmaceuticals, for imaging diverse malignancies other than conventional established tracers.

Recurrent Urinary Bladder Paraganglioma Detected on 68Ga DOTANOC PET/CT.

Urinary bladder paraganglioma constitute only a small fraction of urinary bladder tumors. These rare tumors are well known for recurrences even after many years of surgery. Functional imaging with different radiotracers has been found to be useful to evaluate the extent, metastasis, and recurrence of paragangliomas. We report a case where Ga DOTANOC PET/CT successfully detected recurrence of a paraganglioma in the urinary bladder along with pelvic lymph nodal metastasis.

Fluorothymidine PET/CT in neurolymphomatosis.

Neurolymphomatosis, a rare extranodal lymphoma, may involve the cranial nerves, peripheral nerves, spinal nerve roots, or nerve plexus. F-FDG PET/CT however shows increased FDG uptake in the nerves but is not specific for malignancy. We report a patient with neurolymphomatosis who underwent F-FDG PET/CT and F-fluorothymidine PET/CT where both the scans showed increased tracer uptake in the right sciatic nerve, proven later as neurolymphomatosis on nerve biopsy. Furthermore, the F-FDG avid mediastinal lymph nodes did not show F-fluorothymidine avidity, suggesting an inflammatory etiology.