Evaluation of silicon-astatine exchange reaction by kinetics approach and its applications to the development of alpha-emitting therapeutic agents

2019 Fiscal Year Final Research Report

• Project/Area Number: 17K10459
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Radiation science
• Research Institution: National Institutes for Quantum and Radiological Science and Technology
• Principal Investigator: Watanabe Shigeki 国立研究開発法人量子科学技術研究開発機構, 高崎量子応用研究所 放射線生物応用研究部, 主幹研究員(定常) (10450305)
• Co-Investigator(Kenkyū-buntansha): 山田 圭一 群馬大学, 大学院理工学府, 准教授 (70323334) ; 羽場 宏光 国立研究開発法人理化学研究所, 仁科加速器科学研究センター, チームリーダー (60360624)
• Project Period (FY): 2017-04-01 – 2020-03-31
• Keywords: アスタチン-211 / 標的α線治療 / ケイ素―ハロゲン交換反応 / アミノ酸

Outline of Final Research Achievements

Astatine-211 is one of the promising radionuclides for the Targeted Alpha Therapy (Radionuclide therapy using alpha-emitting radionuclides). The aims of this study are to evaluate the usefulness of silicon-astatine (Si-At) exchange reaction (electrophilic desilylation) by kinetic approach and to synthesize astatinated compounds via the Si-At exchange reaction. We have successfully synthesized an astatinated amino acid (phenylalanine) and benzylguanidine (MABG) in a good yield which is better than those by the conventional astatinated method. Therefore, this study revealed that the Si-At exchange reaction is quite useful for the synthesis of astatinated compounds for the Targeted Alpha Therapy.

Free Research Field

放射化学、有機化学

Academic Significance and Societal Importance of the Research Achievements

標的α線治療は、β線を用いる従来の治療法よりも高い効果が期待されることから、これまで治療が難しかった疾患の治療が期待できる。本研究で検討したケイ素―アスタチン交換反応は、At-211標識化合物を簡便かつ高収率で合成できるため、今後、これまで合成が難しかった化合物の合成が可能になり、ひいては新たな標的α線治療用薬剤の開発につながることが期待できる。