1. Preparation of 177 Lu-PSMA-617 in Hospital Radiopharmacy: Convenient Formulation of a Clinical Dose Using a Single-Vial Freeze-Dried PSMA-617 Kit Developed In-House.
- Author
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Guleria M, Amirdhanayagam J, Sarma HD, Rallapeta RP, Krishnamohan VS, Nimmagadda A, Ravi P, Patri S, Kalawat T, and Das T
- Subjects
- Animals, Dipeptides pharmacokinetics, Drug Compounding methods, Drug Stability, Freeze Drying, Heterocyclic Compounds, 1-Ring pharmacokinetics, Humans, In Vitro Techniques, Lutetium pharmacokinetics, Male, Nuclear Pharmacy methods, Pharmacy Service, Hospital, Positron Emission Tomography Computed Tomography, Prostate-Specific Antigen pharmacokinetics, Prostatic Neoplasms diagnostic imaging, Prostatic Neoplasms pathology, Prostatic Neoplasms, Castration-Resistant diagnostic imaging, Prostatic Neoplasms, Castration-Resistant pathology, Prostatic Neoplasms, Castration-Resistant radiotherapy, Radiochemistry methods, Radiochemistry standards, Radioisotopes pharmacokinetics, Radiopharmaceuticals pharmacokinetics, Rats, Rats, Wistar, Tissue Distribution, Dipeptides isolation & purification, Dipeptides therapeutic use, Heterocyclic Compounds, 1-Ring isolation & purification, Heterocyclic Compounds, 1-Ring therapeutic use, Lutetium isolation & purification, Lutetium therapeutic use, Prostate-Specific Antigen isolation & purification, Prostate-Specific Antigen therapeutic use, Prostatic Neoplasms radiotherapy, Radioisotopes isolation & purification, Radioisotopes therapeutic use, Radiopharmaceuticals isolation & purification, Radiopharmaceuticals therapeutic use
- Abstract
Objective: In the recent time, endoradionuclide therapy for metastatic castration-resistant prostate carcinoma employing
177 Lu-PSMA-617 has yielded encouraging results and several clinical trials with the agent are currently ongoing. Routine preparation of177 Lu-PSMA-617 patient doses can be made simpler and convenient, if the ingredients essential for radiolabeling are made available in a ready-to-use lyophilized form., Methods: PSMA-617 freeze-dried kit was formulated and used for the preparation of177 Lu-PSMA-617 clinical dose with high radiochemical purity using low/medium specific activity177 Lu. Detailed radiochemical studies were performed to determine the maximum activity and volume of177 LuCl3 , which can be added in the kit for the formulation of177 Lu-PSMA-617. Studies were also performed to determine the shelf life of the kit to ensure its long-term usage. Studies were performed in buffer as well as human serum medium to determine the stability of the177 Lu-PSMA-617 complex after storing in respective media up to 7 days postpreparation. About ten patient doses of177 Lu-PSMA-617 were administered, and posttherapy scans were acquired., Results: The formulated freeze-dried kit of PSMA-617 could be radiolabeled with an average percentage radiochemical purity > 98.53 ± 0.38. The freeze-dried kit was found suitable for tolerating up to 0.5 mL of177 LuCl3 (in 0.01 N HCl) and specific activity of 555 MBq/ μ g (15 mCi/ μ g) for the preparation of the patient dose of177 Lu-PSMA-617. The177 Lu-PSMA-617 complex prepared using the freeze-dried kit of PSMA-617 was observed to maintain % radiochemical purity (RCP) of 96.74 ± 0.87 and 94.81 ± 2.66, respectively, even after storing up to 7 days in buffer and human serum, respectively.177 Lu-PSMA-617 prepared using the in-house formulated freeze-dried kit of PSMA-617 exhibited accumulation in metastatic lesions picked up in a pretherapy PET scan. Reduction in number as well as size of lesions was observed in posttherapy scans acquired after two months of administering the first therapeutic dose of177 Lu-PSMA-617., Conclusions: The freeze-dried kit of PSMA-617 could be used for the preparation of177 Lu-PSMA-617 with high radiochemical purity (>98%) in a reproducible manner.177 Lu-PSMA-617 prepared using the developed kit was successfully evaluated in patients suffering from metastatic prostate cancer., Competing Interests: The authors declare that they have no conflict of interests., (Copyright © 2021 Mohini Guleria et al.)- Published
- 2021
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