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Elucidation of renal tubular secretion mechanism of drugs and development of new renal functional methods in nuclear medicine

Research Project

Project/Area Number 18K07747
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 InstitutionKanazawa University

Principal Investigator

Kobayashi Masato  金沢大学, 保健学系, 准教授 (30444235)

Co-Investigator(Kenkyū-buntansha) 川井 恵一  金沢大学, 保健学系, 教授 (30204663)
Project Period (FY) 2018-04-01 – 2021-03-31
Project Status Completed (Fiscal Year 2020)
Budget Amount *help
¥4,420,000 (Direct Cost: ¥3,400,000、Indirect Cost: ¥1,020,000)
Fiscal Year 2020: ¥780,000 (Direct Cost: ¥600,000、Indirect Cost: ¥180,000)
Fiscal Year 2019: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
Fiscal Year 2018: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Keywords核医学 / イメージング / 腎臓 / 薬物トランスポータ / CT造影剤 / SPECT / 薬物トランスポーター / 分子イメージング / 放射線技術学 / 医学物理 / トランスポータ
Outline of Final Research Achievements

Although accurate measurement of renal excretory function is clinically important, the renal tubular secretion mechanism and tubular epithelial cell accumulation have not been fully elucidated. In this study, we develop a nuclear medicine imaging method that can accurately and specifically measure the amount of proximal tubular secretion, and the mechanism of proximal tubular secretion of drugs whose side effects are a problem in clinical examinations. As a result, OAT3 expressed in the basolateral membrane on the tubular epithelial cell vascular side was involved in the renal cortex accumulation of [99mTc]DMSA. In addition, the non-ionic iodine contrast agent Iopamiron is taken up into renal tubular epithelial cells from the tubular lumen side via MATE1 and MATE2-K, and accumulates and stays there. It has been reducing the survival rate of renal cells.

Academic Significance and Societal Importance of the Research Achievements

腎機能の正確かつ特異的に定量測定可能な核医学画像測定法の開発を目指して,臨床画像検査用腎シンチグラフィの一つである[99mTc]DMSAの腎皮質に対する集積機序に有機アニオントランスポーターOAT3が関与していることを解明した.また,臨床検査で腎臓での副作用が問題となっている非イオン性ヨード造影剤イオパミロンの近位尿細管分泌機序にH+/有機カチオンアンチポーターMATE1と2-Kが関わっており,基底膜側の薬物トランスポータの関与がなかったため尿細管上皮細胞に集積することを発見した.

Report

(4 results)
  • 2020 Annual Research Report   Final Research Report ( PDF )
  • 2019 Research-status Report
  • 2018 Research-status Report
  • Research Products

    (11 results)

All 2021 2020 Other

All Int'l Joint Research (2 results) Journal Article (4 results) (of which Int'l Joint Research: 2 results,  Peer Reviewed: 4 results) Presentation (3 results) Patent(Industrial Property Rights) (2 results)

  • [Int'l Joint Research] National Institutes of Health/MD Anderson Cancer Center(米国)

    • Related Report
      2020 Annual Research Report
  • [Int'l Joint Research] テキサス大学MDアンダーソンがんセンター/National Institutes of Health/スタンフォード大学(米国)

    • Related Report
      2018 Research-status Report
  • [Journal Article] Clinical Value of PET/CT with Carbon-11 4DST in the Evaluation of malignant and benign lung tumors.2021

    • Author(s)
      Nishii R, Saga T, Sudo H, Togawa T, Kuyama J, Tani T, Maeda T, Kobayashi M, Iizasa T, Shingyoji M, Itami M, Kawamura K, Hashimoto H, Yamazaki K, Kentaro Tamura K, Higashi T.
    • Journal Title

      Annals of Nuclear Medicine

      Volume: 35 Issue: 2 Pages: 211-222

    • DOI

      10.1007/s12149-020-01554-8

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Assessment of drug transporters involved in the urinary secretion of [99mTc]dimercaptosuccinic acid.2021

    • Author(s)
      Kobayashi M, Mizutani A, Okamoto T, Muranaka Y, Nishi K, Nishii R, Shikano N, Nakanishi T, Tamai I, Kleinerman ES, Kawai K.
    • Journal Title

      Nuclear Medicine and Biology

      Volume: 94-95 Pages: 92-97

    • DOI

      10.1016/j.nucmedbio.2021.01.004

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] [131I]MIBG exports via MRP transporters and inhibition of the MRP transporters improves accumulation of [131I]MIBG in neuroblastoma.2020

    • Author(s)
      Kobayashi M, Mizutani A, Nishi K, Muranaka Y, Nishii R, Shikano N, Nakanishi T, Tamai I, Kleinerman ES, Kawai K.
    • Journal Title

      Nuclear Medicine and Biology

      Volume: 90-91 Pages: 49-54

    • DOI

      10.1016/j.nucmedbio.2020.09.004

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] Transport mechanism and affinity of [99mTc]mercaptoacetyltriglycine ([99mTc]MAG3) on the apical membrane of renal proximal tubule cells.2020

    • Author(s)
      Kobayashi M, Nishi K, Mizutani A, Okudaira H, Nakanishi T, Shikano N, Nishii R, Tamai I, Kawai K.
    • Journal Title

      Nuclear Medicine and Biology.

      Volume: 84-85 Pages: 33-37

    • DOI

      10.1016/j.nucmedbio.2020.01.002

    • Related Report
      2020 Annual Research Report 2019 Research-status Report
    • Peer Reviewed
  • [Presentation] ヒト細胞と感染細菌のシグナルコントラストを利用した細菌感染症画像診断法の検討.2020

    • Author(s)
      村中由香, 大畑周星, 桐谷武明, 仲本恒弥、松榮美希, 湯淺善恵, 水谷明日香, 小林正和, 岡本成史, 川井恵一.
    • Organizer
      第60回日本核医学会学術総会
    • Related Report
      2020 Annual Research Report
  • [Presentation] イメージングによる肝臓の薬物代謝酵素CYP2D6活性定量を目指した新規18F標識画像診断薬の開発2020

    • Author(s)
      桐谷武明, 水谷明日香,鈴木千恵,小林正和,藤田健一,北村正典,國嶋崇隆,間賀田泰寛,川井恵一.
    • Organizer
      第60回日本核医学会学術総会
    • Related Report
      2020 Annual Research Report
  • [Presentation] 大腸菌K-12株における標識アミノ酸の集積と輸送特性の評価.2020

    • Author(s)
      大畑周星,小林正和,村中由佳,仲本恒弥,松榮美希,湯淺善恵,水谷明日香,岡本成史,川井恵一.
    • Organizer
      第60回日本核医学会学術総会
    • Related Report
      2020 Annual Research Report
  • [Patent(Industrial Property Rights)] 有機アニオントランスポーターの機能を測定するための検査薬2021

    • Inventor(s)
      小林正和,川井恵一,水谷明日香,村中由佳.
    • Industrial Property Rights Holder
      小林正和,川井恵一,水谷明日香,村中由佳.
    • Industrial Property Rights Type
      特許
    • Filing Date
      2021
    • Related Report
      2020 Annual Research Report
  • [Patent(Industrial Property Rights)] 薬物代謝酵素活性を測定するための放射性フッ素標識画像診断薬2020

    • Inventor(s)
      川井恵一,国嶋崇隆,小林正和,その他4名.
    • Industrial Property Rights Holder
      川井恵一,国嶋崇隆,小林正和,その他4名.
    • Industrial Property Rights Type
      特許
    • Filing Date
      2020
    • Related Report
      2020 Annual Research Report

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Published: 2018-04-23   Modified: 2022-01-27  

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