Preparation of 177Lu-PSMA-617 in Hospital Radiopharmacy: Convenient Formulation of a Clinical Dose Using a Single-Vial Freeze-Dried PSMA-617 Kit Developed In-House.

Mohini Guleria,Parthasarathy Ravi,Tapas Das,Sailaja Patri,Haladhar D Sarma,Jeyachitra Amirdhanayagam,Tekchand Kalawat,Ramya Priya Rallapeta,Ajit Nimmagadda,V S Krishnamohan

doi:10.1155/2021/1555712

Abstract

Objective In the recent time, endoradionuclide therapy for metastatic castration-resistant prostate carcinoma employing 177Lu-PSMA-617 has yielded encouraging results and several clinical trials with the agent are currently ongoing. Routine preparation of 177Lu-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 of 177Lu-PSMA-617 clinical dose with high radiochemical purity using low/medium specific activity 177Lu. Detailed radiochemical studies were performed to determine the maximum activity and volume of 177LuCl3, which can be added in the kit for the formulation of 177Lu-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 the 177Lu-PSMA-617 complex after storing in respective media up to 7 days postpreparation. About ten patient doses of 177Lu-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 of 177LuCl3 (in 0.01 N HCl) and specific activity of 555 MBq/μg (15 mCi/μg) for the preparation of the patient dose of 177Lu-PSMA-617. The 177Lu-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. 177Lu-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 of 177Lu-PSMA-617. Conclusions The freeze-dried kit of PSMA-617 could be used for the preparation of 177Lu-PSMA-617 with high radiochemical purity (>98%) in a reproducible manner. 177Lu-PSMA-617 prepared using the developed kit was successfully evaluated in patients suffering from metastatic prostate cancer.

Highlights

Prostate cancer is the second most frequently diagnosed cancer in men and the fifth leading cause of cancer-related deaths worldwide [1, 2]
In paper chromatography (PC), carried out using acetonitrile : water (1 : 1 v/v) as the mobile phase, 177Lu-PSMA-617 moved towards the solvent front (Rf = 0:9-1.0), while uncomplexed 177LuCl3 remained at point of spotting (Rf = 0:0-0.1) under identical conditions
Analyses of PC data showed that the 177Lu-PSMA-617 complex could be obtained with >95% radiochemical purity using the freeze-dried PSMA-617 kit

Summary

Introduction

Prostate cancer is the second most frequently diagnosed cancer in men and the fifth leading cause of cancer-related deaths worldwide [1, 2]. According to the GLOBOCAN 2018 estimate, more than 1.3 million patients were expected to be diagnosed with prostate cancer leading to 359,000 associated deaths worldwide during 2018 [3]. Recent success of PSMA (Prostate-Specific Membrane Antigen) ligands labeled with PET (Positron Emission Tomography) radionuclides, with 68Ga, has increased the application of nuclear imaging in the diagnosis of prostate cancer in different clinical settings, such as for primary staging, assessment of therapeutic responses, and treatment planning [4,5,6,7,8,9]. Success of the 177Lu-labeled PSMA ligand, namely, 177Lu-PSMA-617, has opened up a new chapter in the clinical management of prostate cancer, where wellestablished therapeutic efficacy of 177Lu in combination with targeting efficacy of the PSMA-617 ligand yielded encouraging outcomes [10,11,12,13,14,15,16,17,18,19,20]

Methods

Results

Conclusion