Development of 211At-labeled amino acid derivative targeting LAT1 as a novel alpha-emitting radiopharmaceutical

2017 Fiscal Year Final Research Report

• Project/Area Number: 16K21603
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Radiation science; Tumor therapeutics
• Research Institution: National Institutes for Quantum and Radiological Science and Technology
• Principal Investigator: Ohshima Yasuhiro 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, 主任研究員(定常) (00588676)
• Research Collaborator: WATANABE Satoshi ; SUZUKI Hiroyuki ; SAKASHITA Tetsuya
• Project Period (FY): 2016-04-01 – 2018-03-31
• Keywords: α線放出核種 / 211At / 2-AAMP / L型アミノ酸トランスポーター1（LAT1) / がん

Outline of Final Research Achievements

In this study, we synthesized 2-[211At]astato-α-methyl-L-phenylalanine (2-AAMP) and evaluated its usefulness as a novel radiopharmaceutical targeting L-type amino acid transporter 1 (LAT1). 2-AAMP was successfully synthesized with high yield and purity by labelling the precursor with 211At in the presence of oxidant. 2-AAMP was taken up to tumor cells via LAT1, and induced DNA double strand break, growth inhibition and cell death. 2-AAMP was stable in vivo, and further accumulated and retained in tumor. On the other hand, 2-AAMP was rapidly cleared from normal organs in mice. These results suggest that 2-AAMP might be useful as a novel α-emitting radiopharmaceutical.

Free Research Field

放射線生物学、放射性医薬品