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Background <p>[<sup>211</sup>At]<i>m</i>-Astatobenzylguanidine ([<sup>211</sup>At]MABG) has demonstrated potent antitumor efficacy in preclinical models of malignant neuroendocrine tumours including neuroblastoma and pheochromocytoma/paraganglioma. 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 [<sup>211</sup>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 [<sup>211</sup>At]MABG suitable for clinical translation.</p> Results <p><sup>211</sup>At was produced via the <sup>209</sup>Bi(α,2n)<sup>211</sup>At nuclear reaction using a cyclotron, with <sup>210</sup>At formation minimised by precise control of the alpha particle energy. The resulting product was purified using an automated dry distillation system. [<sup>211</sup>At]MABG was synthesised using the COSMiC-Mini automated synthesiser in 28.2 ± 2.8&#xa0;min from initial <sup>211</sup>At activities of up to 586.1&#xa0;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.</p> Conclusions <p>In this study, we established a reliable and scalable production methodology for [<sup>211</sup>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 [<sup>211</sup>At]MABG in targeted alpha therapy.</p>

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Production of 211At and automated radiosynthesis of [211At]MABG via electrophilic astatodesilylation

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2025年8月5日

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  • Yuto Kondo,
  • Taiki Joho,
  • Shigenori Sasaki,
  • Kazumasa Mochizuki,
  • Naoko Hasegawa,
  • Naoyuki Ukon,
  • Ken-ichi Nishijima,
  • Kohshin Washiyama,
  • Hiroshi Tanaka,
  • Tatsuya Higashi,
  • Noriko S. Ishioka,
  • Kazuhiro Takahashi

摘要

Background

[211At]m-Astatobenzylguanidine ([211At]MABG) has demonstrated potent antitumor efficacy in preclinical models of malignant neuroendocrine tumours including neuroblastoma and pheochromocytoma/paraganglioma. 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 [211At]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 [211At]MABG suitable for clinical translation.

Results

211At was produced via the 209Bi(α,2n)211At nuclear reaction using a cyclotron, with 210At formation minimised by precise control of the alpha particle energy. The resulting product was purified using an automated dry distillation system. [211At]MABG was synthesised using the COSMiC-Mini automated synthesiser in 28.2 ± 2.8 min from initial 211At 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 [211At]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 [211At]MABG in targeted alpha therapy.