Background <p>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&amp;T for clinical use. [¹⁷⁷Lu]Lu-PSMA I&amp;T is a radioligand therapy (RLT) that targets prostate-specific membrane antigen (PSMA), which is overexpressed in metastatic and castration-resistant prostate cancer.</p> Results <p>This work delineates the development and validation of analytical methodologies for the automated production of [¹⁷⁷Lu]Lu-PSMA I&amp;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&amp;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&amp;T preparations at room temperature, a development that facilitates the potential subcontracting of [¹⁷⁷Lu]Lu-PSMA I&amp;T production to other medical facilities.</p> Conclusions <p>The findings of this study underscore the potential of [¹⁷⁷Lu]Lu-PSMA I&amp;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.</p>