Development of radiotheranostics agent using Fab fragment of anti-regulatory T cells

2019 Fiscal Year Final Research Report

• Project/Area Number: 17H04258
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Radiation science
• Research Institution: Chiba University
• Principal Investigator: Uehara Tomoya 千葉大学, 大学院薬学研究院, 教授 (10323403)
• Co-Investigator(Kenkyū-buntansha): 藤井 博史 国立研究開発法人国立がん研究センター, 先端医療開発センター, 分野長 (80218982) ; 中野 直子 東京理科大学, 研究推進機構生命医科学研究所, 准教授 (90222166)
• Project Period (FY): 2017-04-01 – 2020-03-31
• Keywords: 核医学治療 / Treg

Outline of Final Research Achievements

We have developed the gallium-67/68 labeling agent, NOTA-MVK-Mal, for antibody fragment to reduce renal radioactivity levels so far. In this study, we investigated the applicability of this labeling agent to the therapeutic radionuclide, cupper-64, using anti-c-kit antibody Fab fragment. In in vitro study, the recognition of brush border enzymes to the Cu-64 labeled probe was reduced compared with Ga-67 labeled counterpart. However, in the biodistribution study using normal mice, the renal radioactivity levels after injection of Cu-64 labeled Fab fragments using this labeling agent were similar to those of Ga-67 labeled Fab fragments. These results suggested that the this radiolabeling agent would be applicable to the Cu-64. Furthermore, the reduction of renal radioactivity levels was observed even if Fab fragment against a regulatory T cells (CD25) as Fab fragment were used.

Free Research Field

核医学治療

Academic Significance and Societal Importance of the Research Achievements

従来、診断用の放射性核種である放射性ガリウムを用いて開発した腎臓の放射活性を低減する抗体Fabフラグメントの標識薬剤が治療用の放射性薬剤である銅-64でも適用可能であることを示したことは、個別化医療につながるradiotheranosticsへ、本標識薬剤が適用可能であることを実証したと考えている。また、銅-64はガリウム-68に比べ半減期の長いPET核種であり、Fabを用いたPETから治療への応用がより一層期待でき、精密な診断と治療を行うradiotheranosticsに大いに貢献できると考えている。