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Development of nuclear imaging probes for detection of tumor associated macrophages

Research Project

Project/Area Number 19K08096
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Review Section Basic Section 52040:Radiological sciences-related
Research InstitutionKyoto University

Principal Investigator

SHIMIZU YOICHI  京都大学, 医学研究科, 講師 (90634212)

Project Period (FY) 2019-04-01 – 2023-03-31
Project Status Completed (Fiscal Year 2022)
Budget Amount *help
¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000)
Fiscal Year 2021: ¥910,000 (Direct Cost: ¥700,000、Indirect Cost: ¥210,000)
Fiscal Year 2020: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
Fiscal Year 2019: ¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000)
Keywords腫瘍随伴マクロファージ / 核医学
Outline of Research at the Start

固形腫瘍組織に存在する腫瘍随伴マクロファージ(TAM)のM2型は腫瘍細胞の増殖、転移や腫瘍組織内の血管新生を促進し、腫瘍の悪性化に関与していることが最近報告されている。そこで本研究では、M2型マクロファージに高発現するCD206、Tissue Factor(TF)に対して特異的に結合する68Ga標識PET診断剤を開発し、これまで適切な手法のなかった固形腫瘍の性状診断を可能とする核医学診断法を確立する。

Outline of Final Research Achievements

It has been recently reported that M2 type of tumor-associated macrophages (TAM), which exist in solid tumor tissues, promote tumor cell proliferation, metastasis, and angiogenesis in tumor tissues, and are involved in tumor malignant transformation. In this study, we focused on the fact that mannose receptor (CD206) and Tissue Factor (TF) are highly expressed in M2-type macrophages and used the molecular design concept of "functional unit-bound multifunctional molecular probes" to develop peptides that bind specifically to CD206 and TF and can be synthesized chemically, We developed a peptide-based nuclear medicine diagnostic agent that binds specifically to CD206 and TF and can be chemically synthesized, aiming to develop a nuclear medicine diagnostic method that enables the diagnosis of solid tumors, for which no appropriate method has been available so far.

Academic Significance and Societal Importance of the Research Achievements

本研究では、がんの悪性度化に関与するM2型TAMに高発現するTFおよびCD206を標的とした核医学診断剤の開発を行った。今回開発した各薬剤は体内動態等にまだ改善の余地があるものの、M2型TAMのがん悪性度化に関する研究や、TAM標的抗がん剤開発等において、本薬剤を用いた核医学イメージングによりTAMの性状鑑別(M2型分化度など)の評価が可能となり、今後のがん診断、治療研究に貢献できる可能性があると考えている。

Report

(5 results)
  • 2022 Annual Research Report   Final Research Report ( PDF )
  • 2021 Research-status Report
  • 2020 Research-status Report
  • 2019 Research-status Report
  • Research Products

    (7 results)

All 2022 2021 2020

All Journal Article (1 results) (of which Peer Reviewed: 1 results,  Open Access: 1 results) Presentation (6 results) (of which Invited: 1 results)

  • [Journal Article] Development of a hydroxamamide-based bifunctional chelating agent to prepare technetium-99m-labeled bivalent ligand probes2021

    • Author(s)
      Shimizu Yoichi、Ando Masato、Iikuni Shimpei、Watanabe Hiroyuki、Ono Masahiro
    • Journal Title

      Scientific Reports

      Volume: 11 Issue: 1 Pages: 18714-18714

    • DOI

      10.1038/s41598-021-98235-x

    • Related Report
      2021 Research-status Report
    • Peer Reviewed / Open Access
  • [Presentation] [18F]F-AraGの臨床利用に向けた多目的合成装置による製造法の検討2022

    • Author(s)
      志水陽一,野橋智美,中本裕士
    • Organizer
      第62回日本核医学会学術総会
    • Related Report
      2022 Annual Research Report
  • [Presentation] Optimizing of automated synthesis of 68Ga-DOTATOC with Ga-68 produced by cyclotron liquid target system for clinical use2022

    • Author(s)
      Shimizu Y, Kobayashi K, Kumano M, Okamura A, Saga T, Nakamoto Y.
    • Organizer
      13th Congress of the World Federation of Nuclear Medicine and Biology
    • Related Report
      2022 Annual Research Report
  • [Presentation] 次世代核医学診療に対応可能なサイクロトロン施設の構築2022

    • Author(s)
      志水陽一
    • Organizer
      PETサマーセミナー2022 in 甲府
    • Related Report
      2022 Annual Research Report
    • Invited
  • [Presentation] サイクロトロンliquid target systemにて製造するGa-68を用いた68Ga-DOTATOC自動合成法の検討2021

    • Author(s)
      1.志水陽一,小林敬三,熊野充繁,岡村明彦,石守崇好,佐賀恒夫,中本裕士
    • Organizer
      第61回日本核医学会学術総会
    • Related Report
      2021 Research-status Report
  • [Presentation] Ga-68標識薬剤の安定供給に向けたサイクロトロン liquid target system によるGa-68製造法の検討2021

    • Author(s)
      5.志水陽一,小林敬三,熊野充繁,岡村明彦,石守崇好,佐賀恒夫,中本裕士
    • Organizer
      第3 回日本核医学会 近畿支部会
    • Related Report
      2021 Research-status Report
  • [Presentation] 99mTc標識2価リガンドを容易に調製可能とするHydroxamamide母核二官能性キレート剤の開発2020

    • Author(s)
      安藤正登,志水陽一,飯國慎平,渡邊裕之,小野 正博
    • Organizer
      第60回日本核医学会学術総会
    • Related Report
      2020 Research-status Report

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Published: 2019-04-18   Modified: 2024-01-30  

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