Production of 211At and Automated Radiosynthesis of [211At]MABG via Electrophilic Astatodesilylation

Background: [ ²¹¹ At] m -Astatobenzylguanidine ([ ²¹¹ At]MABG) has demonstrated potent antitumor efficacy in preclinical models of malignant neuroendocrine tumours. The high linear energy transfer and short tissue penetration range of alpha particles enable highly localized cytotoxic effects, potentially overcoming therapeutic limitations associated with conventional beta-emitting radiopharmaceuticals. However, under clinical-scale (i.e., high radioactivity) conditions, the efficient and stable production of [ ²¹¹ At]MABG has been hindered by radiolytic degradation during the manufacturing process limiting the availability of reliable methods offering high radiochemical yield and purity. In this study, we aimed to develop a scalable production methodology for [ ²¹¹ At]MABG suitable for clinical translation. Results: ²¹¹ At was produced via the ²⁰⁹ Bi(α,2n) ²¹¹ At nuclear reaction using a cyclotron, with ²¹⁰ At formation minimised by precise control of the alpha particle energy. The resulting product was purified using an automated dry distillation system. [ ²¹¹ At]MABG was synthesised using the COSMiC-Mini automated synthesiser in 28.2 ± 2.8 min from initial ²¹¹ At activities of up to 586.1 MBq. The radiochemical yield and purity were 80.3 ± 4.4% (decay-corrected RCY: 84.0 ± 4.5%) and 99.0 ± 0.7%, respectively (n = 6). The addition of sodium ascorbate as a radical scavenger contributed to maintaining a high radiochemical yield and purity during large-scale production. The final product was obtained as a sterile solution. Conclusions: In this study, we established a reliable and scalable production methodology for [ ²¹¹ At]MABG, consistently achieving high radiochemical yield and purity across a wide range of radioactivity levels through optimization of the automated radiosynthesis process and the use of radiolytic stabilizers. This approach provides a solid technical foundation for the clinical application of [ ²¹¹ At]MABG in targeted alpha therapy for neuroendocrine tumours.