Priya Bhusari

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.

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.

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.

Novel use of 177Lu-DOTA-RGD2 in treatment of 68Ga-DOTA-RGD2-avid lesions in papillary thyroid cancer with TENIS

Thyroglobulin elevation with negative I scintigraphy (TENIS) in patients with differentiated thyroid carcinoma (DTC) poses a unique management challenge to the physician due to limited treatment modalities. Treatment with chemo-radiation, redifferentiation therapy, tyrosine kinase inhibitors and peptide receptor radionuclide therapy (PRRT) using somatostatin analogues have shown very insignificant clinical benefits with high incidence of adverse effects [1]. Arginylglycylaspartic acid (RGD) tripeptide sequence, having very high specificity towards αvβ3 integrin, is over-expressed on the tumor vasculature, including DTC and can be used as a theranostic agent [2–4]. We present a 54-year-old woman with papillary carcinoma thyroid who developed TENIS syndrome after receiving 500 GBq of I in cumulative doses. She experienced significant adverse effects with no clinical improvement on sorafenib therapy for 1 year and presented with severe pain and a palpable hard mass in the pre-sternal region. GaDOTA-RGD2 PET/CT was performed to evaluate disease extent and for pre-therapy assessment. The maximum intensity projection (MIP) image (a) and transaxial fused PET/CT images showed increased tracer uptake in the thyroid remnant [maximum standardized uptake value (SUVmax) = 4.7] with cervical lymph nodes (b), mediastinal lymph node (c; SUVmax = 8.4), lytic skeletal lesions with soft tissue component in the sternum (c; SUVmax = 7.8) and left iliac bone (d; SUVmax = 8.4) and multiple lung nodules (e). The patient received 5.5 GBq of Lu-DOTA-RGD2 with post-therapy whole-body images in anterior (f) and posterior (g) views revealing the overall distribution of LuDOTA-RGD2 and transaxial fused SPECT/CT images (h–k) showing tracer uptake at sites corresponding to Ga-DOTA-RGD2 -avid lesions. The patient was followed up at 4 months post-therapy, with significant pain relief and reduced pre-sternal swelling suggesting clinical benefit. Post-therapy follow-up Ga-DOTARGD2 PET/CT MIP image (l) and transaxial fused PET/CT images showed tracer uptake in the thyroid remnant (SUVmax = 3.0 vs. 4.7) with cervical lymph nodes (m), mediastinal lymph node (n; SUVmax = 7.7 vs. 8.4), lytic skeletal lesions with significant reduction in soft tissue component in the sternum (n; SUVmax = 6.6 vs. 7.8) and left iliac bone (o; SUVmax 8.1 vs. 8.4) and multiple lung nodules (p), suggesting response to therapy. To the best of our knowledge, this is the first reported theranostics using Ga-DOTA-RGD2 and Lu-DOTA-RGD2 and can be a stepping stone for future studies.