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Background <p>Terbium‑161 (<sup>161</sup>Tb) 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 [<sup>161</sup>Tb]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.</p> Results <p>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.</p> Conclusion <p>A robust, rapid, and fully automated GMP-compliant method for [<sup>161</sup>Tb]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 [<sup>161</sup>Tb]Tb-labeled PSMA radioligands for improved management of advanced prostate cancer.</p>

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

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2026年6月23日

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  • David Kryza,
  • Pierre Le Fur,
  • Jean Noël Badel,
  • Clément Morgat,
  • Fouzi Khayi,
  • Anne-Laure Giraudet

摘要

Background

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.

Results

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.

Conclusion

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.