Development of radiotheranostic agents targeting neuroendocrine tumor: Cu-64-labeled somatostatin derivatives containing a novel amino acid ATSMaa

2018 Fiscal Year Final Research Report

• Project/Area Number: 17K16491
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Radiation science
• Research Institution: Suzuka University of Medical Science
• Principal Investigator: Fujisawa Yutaka 鈴鹿医療科学大学, 薬学部, 助手 (30511993)
• Project Period (FY): 2017-04-01 – 2019-03-31
• Keywords: 神経内分泌腫瘍 / 次世代診断／治療薬開発 / ATSMaa

Outline of Final Research Achievements

Radiolabeled somatostatin (SST) analogues targeting SST receptor-2 are useful for diagnosis and therapy of neuroendcrine tumor (NET). The aim of our study is to develop a novel theranostic agent which enables to perform both diagnosis and therapy of NET, we had previously synthesized novel Cu-64-labeled SST analogues. In this study, we designed ATSMaa, a Cu(II)-chelatable amino acid, and synthesized novel ATSMaa-containing SST derivatives with the purpose of improving the physical and biological properties of previous compounds. A novel ATSMaa-containing SST derivative possessed higher hydrophilicity and higher affinity with SST receptor-2 than previous compounds. Additionally, it was revealed that a novel derivative induced higher accumulation to target tumor over a prolonged period of time and lower accumulation to some of undesirable organs in NET model mice.

Free Research Field

創薬錯体化学

Academic Significance and Societal Importance of the Research Achievements

日本における神経内分泌腫瘍(NET)に対する放射性医薬品を用いた診断／治療は、欧州に比べ遅れており、薬剤の種類も不十分で薬剤選択の面で難を生じる可能性は否めず、次世代のNET診断／治療薬の開発が望まれる。本研究にて開発した新規アミノ酸ATSMaa含有SST誘導体は、NETモデルマウスを用いた検討において、過去に合成、評価した化合物に比べて良好な結果を示した。更なる構造最適化により、優れたSST誘導体開発につながると期待できる。また、ATSMaaは、悪性腫瘍を標的とした放射性Cu含有診断／治療用ペプチド性薬剤に対して広範囲に応用可能なアミノ酸として、本研究においてその有益性を示せたものと考える。