An example of theranostic in CHU Grenoble Alpes with the implementation of ¹⁷⁷Lu-PSMA-1

Prostate Specific Membrane Antigen (PSMA) is a highly relevant target in nuclear medicine due to its overexpression in prostate cancer. The ⁶⁸Ga/¹⁷⁷Lu-PSMA combination is a theranostic agent for the detection and treatment of tumors overexpressing the PSMA target. Eligibility criterion of ¹⁷⁷Lu- PSMA-1 therapy are a progressive disease after chemotherapy and a second-generation hormonotherapy and a high positive PSMA PET/CT up-take. In order to be authorized to carry out this type of treatment, French radiopharmacies must draft and submit an Investigational Medicinal Product Dossier (IMPD) to the national agency for medicines and health products. This requirement ensured pharmaceutical quality for radiopharmaceutical drugs without a marketing authorization. Part of this IMPD is intended for analytical methods validation in order to determine the radiochemical purity (RCP) by High Performance Liquid Chromatography (HPLC) and Thin Layer Chromatography (TLC) methods. The results obtained demonstrated the robustness and reliability of the HPLC and TLC analytical methods for the evaluation of the RCP of ¹⁷⁷Lu-PSMA-1. A validation of the aseptic process for the preparation of ¹⁷⁷Lu-PSMA1 through a media fill test, a sterility test, a bacterial endotoxins test, a pre-filtration bioburden assessment and a filter integrity test, was performed. Finally, three production batches were performed with an automated synthesis device and we validated all the required quality controls. This work enabled the drafting and validation of the ¹⁷⁷Lu-PSMA-1's DME, which was accepted by the French national agency for medicines and health products in June 2021. (author)