First Automated Radiosynthesis of [161Tb]Tb-PSMA-I&T in Taiwan Using the iPHASE MultiSyn Synthesizer

¹Fan-Chieh Meng, ¹Chi-Wei Chang, ¹Arsyangela Verena, ¹Ya-Ting Huang,¹Ya-Yao Huang^*

¹R&D department, Primo Biotechnology Co., Ltd., Taipei, Taiwan

Introduction: ¹⁷⁷Lu-PSMA-I&T, which targets the prostate-specific membrane antigen (PSMA), has demonstrated effectiveness in treating patients with metastatic castration-resistant prostate cancer (mCRPC). Compared to Lutetium-177, Terbium-161 has a similar half-life and decay characteristics, but also releases a significant number of internal conversion (IC) and Auger electrons (AE), which can deliver higher radiation doses and are suitable for eradicating small tumor lesions and micro-metastatic disease while minimizing collateral damage to surrounding healthy tissues. Here, we report the fully automated radiosynthesis of ¹⁶¹Tb-PSMA-I&T on the iPHASE MultiSyn synthesizer and compare its results with those from ¹⁷⁷Lu-PSMA-I&T.

Method: PSMA-I&T precursor was purchased from ABX (Radeberg, Germany); ¹⁶¹TbCl₃ in 0.05 M HCl was obtained from TERTHERA (Breda, The Netherlands). MultiSyn cassette and reagent kits were purchased from iPHASE Technologies (Melbourne, Australia). The precursor (0.74 µg/mCi) was reacted with ¹⁶¹TbCl₃ in 0.3 M sodium acetate buffer (pH 5.0) and heated at 95 °C for 28 min. The reaction mixture was then formulated by adding sterile water for injection containing sodium L-ascorbate (500 mg) and DTPA (1 mg), followed by sterile filtration into a product vial. The radiochemical purity (RCP) of the final product was determined using iTLC and HPLC.

Results: ¹⁶¹Tb-PSMA-I&T was successfully synthesized on the iPHASE MultiSyn synthesizer. The radiochemical yield (RCY) exceeded 90%, with a total synthesis time of approximately 54 minutes, a final product volume of 12 mL, and a pH of 5.0. The RCP by HPLC was ≥95%, and the fraction of unreacted ¹⁶¹Tb determined by iTLC (R_f = 0.9–1.0) was ≤5%. In comparison to ¹⁷⁷Lu-PSMA-I&T, similar radiochemical purity was achieved without the addition of gentisic acid. Furthermore, the radiochemical yield increased by about 10%, which we think is due to the additional 12 minutes of reaction time, despite differences in the products. It may give us insights into improving the radiochemical yield of ¹⁷⁷Lu-PSMA-I&T in the future.

Conclusions: The first fully automated synthesis of ¹⁶¹Tb-PSMA-I&T on the iPHASE MultiSyn has been successfully established in Taiwan. Stability studies at high activity concentrations are currently underway to ensure compliance with clinical criteria.