Fully GMP-complient radiosynthesis of [161Tb]Tb-PSMA-1 using the miniAiO synthesizer for clinical translation
EJNMMI Radiopharmacy and Chemistry. 2026-06-23; :
DOI: 10.1186/s41181-026-00467-7
1. EJNMMI Radiopharm Chem. 2026 Jun 23. doi: 10.1186/s41181-026-00467-7. Online
ahead of print.
Fully GMP-complient radiosynthesis of [(161)Tb]Tb-PSMA-1 using the miniAiO
synthesizer for clinical translation.
Kryza D(1), Le Fur P(2), Badel JN(2)(3), Morgat C(4)(5), Khayi F(2), Giraudet AL(2).
Author information:
(1)Service de Médecine Nucléaire Lumen, Centre Léon Bérard, 69343, Lyon Cedex
08, France. .
(2)Service de Médecine Nucléaire Lumen, Centre Léon Bérard, 69343, Lyon Cedex
08, France.
(3)CREATIS, CNRS UMR 5220, INSERM U 1044, Université de Lyon, INSA-Lyon,
Université Lyon 1, Lyon, France.
(4)Nuclear Medicine & Radiopharmacy Department, Bordeaux University Hospital,
Bordeaux, France.
(5)INCIA, University of Bordeaux, CNRS, EPHE, UMR 5287, Bordeaux, France.
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.
© 2026. The Author(s).
DOI: 10.1186/s41181-026-00467-7
PMID: 42334711
Conflict of interest statement: Declarations. Ethics approval and consent to
participate: Not applicable. Consent for publication: Not applicable. Competing
interests: The authors declare that they have no competing interests.