GMP-compliant automated synthesis and quality control of [177Lu]Lu-PSMA-I&T using the GAIA/LUNA Elysia-Raytest module for the treatment of metastatic castration-resistant prostate cancer

Prostate cancer (PCa) has been identified as the most prevalent form of cancer among males and the third leading cause of death from cancer in the European male population. Early-stage PCa can be treated with prostatectomy and radiotherapy, whereas metastatic cases require androgen deprivation therapy and may benefit from targeted radionuclide therapy (TRT). The objective of our research is to develop and validate an automated production of [177Lu]Lu-PSMA I&T for clinical use. [177Lu]Lu-PSMA I&T is a radioligand therapy (RLT) that targets prostate-specific membrane antigen (PSMA), which is overexpressed in metastatic and castration-resistant prostate cancer. This work delineates the development and validation of analytical methodologies for the automated production of [177Lu]Lu-PSMA I&T with a GAIA-LUNA device from Elysia, in addition to the quality control measures implemented to ensure compliance with Good Manufacturing Practices and the European Pharmacopoeia. Three validation batches were produced, and the investigational medicinal product dossier was submitted to the French National Agency of Medicine and Health Products Safety (ANSM) for authorization. PSMA-I&T was radiolabeled with 177Lu using an automated radiosynthesis device, the GAIA-LUNA, from Elysia. Furthermore, we demonstrated the 72-h stability of the [177Lu]Lu-PSMA I&T preparations at room temperature, a development that facilitates the potential subcontracting of [177Lu]Lu-PSMA I&T production to other medical facilities. The findings of this study underscore the potential of [177Lu]Lu-PSMA I&T as a therapeutic option for patients with metastatic castration-resistant prostate cancer (mCRPC) who have contraindications to chemotherapy or hormonotherapy, and highlight the importance of implementing rigorous quality control measures in the development of radiopharmaceuticals.