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Development of nuclear medicine imaging technology in the diagnosis of primary aldosteronism

Research Project

Project/Area Number 20K08061
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 Pharmaceutical University

Principal Investigator

KIMURA HIROYUKI  京都薬科大学, 薬学部, 准教授 (50437240)

Project Period (FY) 2020-04-01 – 2023-03-31
Project Status Completed (Fiscal Year 2022)
Budget Amount *help
¥4,420,000 (Direct Cost: ¥3,400,000、Indirect Cost: ¥1,020,000)
Fiscal Year 2022: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2021: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2020: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Keywordsアルドステロン産生腺腫 / CYP11B2 / イメージングプローブ / PET / SPECT / 原発性アルドステロン症 / 核医学検査法
Outline of Research at the Start

原発性アルドステロン症(PA)は、高血圧患者の約5-6%を占め、代表的な二次性高血圧の一つである。PAは主にアルドステロン産生腺腫(APA)と特発性アルドステロン症に大別される。APAの局在診断には副腎静脈サンプリングが必須であるが、技術的に成功率が高い施設が限られており、また、患者さんへの負担も大きく、代替の簡便な局在診断法の開発が望まれている。そこで我々は、核医学イメージング技術を応用した、APAの新しい診断法の開発を目指す。

Outline of Final Research Achievements

To develop a new radiolabeled probe for PET (Positron Emission Tomography) and SPECT (Single Photon Emission Computed Tomography) that can specifically detect aldosterone synthesis-related enzyme CYP11B2, we have developed a new probe based on the structural information of previously reported imaging probes. The synthesized compounds were evaluated for their inhibitory activity against CYP11B1 and CYP11B2, and a compound with high specificity for CYP11B2 was successfully obtained. From the evaluation of the distribution kinetics of the candidate compounds in mice, we succeeded in obtaining compounds that showed high accumulation in the adrenal gland. Finally, we performed an ARG (autoradiography) on a candidate compounds using tissue sections of an aldosterone-producing adenoma provided by a patient, and found a compound that strongly accumulated at sites where CYP11B2 was positive by immunohistochemistry.

Academic Significance and Societal Importance of the Research Achievements

原発性アルドステロン症(PA)は、高血圧患者の約5-6%を占め、代表的な二次性高血圧の一つである。PAは主にアルドステロン産生腺腫(APA)と特発性アルドステロン症に大別される。APAの局在診断には副腎静脈サンプリングが必須であるが、技術的に成功率が高い施設が限られており、また、患者さんへの負担も大きく、代替の簡便な局在診断法の開発が望まれている。新規分子イメージングプローブに基づく新たなAPAの検査法を開発できれば、日本発・世界初の普及可能な検査として、多くの患者を治療に結びつけることが可能となる。

Report

(2 results)
  • 2022 Final Research Report ( PDF )
  • 2020 Research-status Report
  • Research Products

    (4 results)

All 2021 2020 Other

All Journal Article (3 results) (of which Int'l Joint Research: 1 results,  Peer Reviewed: 3 results,  Open Access: 2 results) Remarks (1 results)

  • [Journal Article] Copper-mediated radioiodination reaction through aryl boronic acid or ester precursor and its application to direct radiolabeling of a cyclic peptide2021

    • Author(s)
      Yuto Kondo, Hiroyuki Kimura, Chiaki Fukumoto, Yusuke Yagi, Yasunao Hattori, Hidekazu Kawashima, Hiroyuki Yasui
    • Journal Title

      Journal of Labelled Compounds and Radiopharmaceuticals

      Volume: - Issue: 8 Pages: 336-345

    • DOI

      10.1002/jlcr.3925

    • Related Report
      2020 Research-status Report
    • Peer Reviewed
  • [Journal Article] Synthesis of 18F-labeled streptozotocin derivatives and an in-vivo kinetics study using positron emission tomography2020

    • Author(s)
      Arimitsu Kenji、Yagi Yusuke、Koshino Kazuhiro、Nishito Yukina、Higuchi Takahiro、Yasui Hiroyuki、Kimura Hiroyuki
    • Journal Title

      Bioorganic & Medicinal Chemistry Letters

      Volume: 30 Issue: 17 Pages: 127400-127400

    • DOI

      10.1016/j.bmcl.2020.127400

    • Related Report
      2020 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Automatic radioisotope manipulation for small amount of nuclear medicine using an EWOD device with a dimple structure2020

    • Author(s)
      Katsuo Mogi, Hiroyuki Kimura, Yuto Kondo, Tomoya Inoue, Shungo Adachi, Tohru Natsume
    • Journal Title

      Royal Society Open Science

      Volume: -

    • Related Report
      2020 Research-status Report
    • Peer Reviewed / Open Access
  • [Remarks] 京都薬科大学 代謝分析学分野

    • URL

      https://labo.kyoto-phu.ac.jp/taisya/

    • Related Report
      2020 Research-status Report

URL: 

Published: 2020-04-28   Modified: 2024-01-30  

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