Fully GMP-complient radiosynthesis of [¹⁶¹Tb]Tb-PSMA-1 using the miniAiO synthesizer for clinical translation

Terbium‑161 (¹⁶¹Tb) is an emerging radionuclide for targeted radionuclide therapy that combines β⁻ emissions with short‑range conversion and Auger electrons, increasing its efficacy against micrometastatic and low‑volume prostate cancer. This study aimed to develop, optimize, and validate a fully automated good manufacturing practice (GMP)-compliant radiosynthesis of [¹⁶¹Tb]Tb-PSMA‑1 for clinical application. Radiolabeling parameters were systematically investigated via different buffer systems (acetate, ammonium acetate, and ascorbate), labeling temperatures (24-95 °C), and ethanol supplementation. Process validation was performed on three independent batches produced under routine conditions (7.4-11.5 GBq) via a Trasis MiniAiO synthesizer. Comprehensive quality control included radionuclidic identification, radiochemical purity (RCP), pH, sterility, endotoxin testing, and container-content interaction assessment.

Efficient radiolabeling was achieved under all the tested conditions, with RCPs consistently exceeding 97%. Optimal performance was observed when ascorbate buffer was used at 95 °C, yielding approximately 99% RCP at the end of synthesis. The addition of 40% (V/V) ethanol improved both the labeling efficiency and radiochemical stability, enabling high RCP even at lower temperatures. The final formulation demonstrated excellent stability, maintaining RCP ≥ 97.5% up to 48 h post-synthesis. All validation batches met predefined release criteria in accordance with Ph. Eur. Monograph radiopharmaceutical preparations. The total synthesis time was less than 30 min.

A robust, rapid, and fully automated GMP-compliant method for [¹⁶¹Tb]Tb-PSMA‑1 production was successfully established. The high radiochemical purity, stability, and reproducibility support its suitability for routine clinical use and decentralized distribution. This work represents a key step toward the clinical translation of [¹⁶¹Tb]Tb-labeled PSMA radioligands for improved management of advanced prostate cancer.