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

Research Project

Project/Area Number 17H04258
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypeSingle-year Grants
Section一般
Research Field Radiation science
Research InstitutionChiba 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
Project Status Completed (Fiscal Year 2019)
Budget Amount *help
¥16,640,000 (Direct Cost: ¥12,800,000、Indirect Cost: ¥3,840,000)
Fiscal Year 2019: ¥5,200,000 (Direct Cost: ¥4,000,000、Indirect Cost: ¥1,200,000)
Fiscal Year 2018: ¥5,200,000 (Direct Cost: ¥4,000,000、Indirect Cost: ¥1,200,000)
Fiscal Year 2017: ¥6,240,000 (Direct Cost: ¥4,800,000、Indirect Cost: ¥1,440,000)
Keywords核医学治療 / Treg / Treg細胞 / Treg抗体 / 放射線 / 免疫学 / 癌 / 制御性T細胞 / がん免疫 / 内用放射線治療
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.

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。

Report

(4 results)
  • 2019 Annual Research Report   Final Research Report ( PDF )
  • 2018 Annual Research Report
  • 2017 Annual Research Report
  • Research Products

    (1 results)

All 2019

All Presentation (1 results)

  • [Presentation] 腎放射活性の低減に刷子縁膜酵素を利用した抗体フラグメント標識薬剤のCu-64への応用2019

    • Author(s)
      喜瀬翔太、上原知也、小林まどか、鈴木博元、荒野泰
    • Organizer
      第3回日本核医学会分科会放射性医薬品科学研究会
    • Related Report
      2019 Annual Research Report

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Published: 2017-04-28   Modified: 2021-02-19  

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