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Investigation of Redox Metabolic Pathways in Tumors via Hyperpolarized MRI and High-Field NMR

Research Project

Project/Area Number 22K07247
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Review Section Basic Section 50020:Tumor diagnostics and therapeutics-related
Research InstitutionGifu University

Principal Investigator

Nozswa Asae  岐阜大学, 大学院医学系研究科, 招へい教員 (90802786)

Co-Investigator(Kenkyū-buntansha) 兵藤 文紀  岐阜大学, 大学院医学系研究科, 教授 (10380693)
松尾 政之  岐阜大学, 大学院医学系研究科, 教授 (40377669)
ABDELAZIMELSAYED ABDELAZIMELHELALY  岐阜大学, 大学院医学系研究科, 研究員 (50939270)
Project Period (FY) 2022-04-01 – 2025-03-31
Project Status Completed (Fiscal Year 2024)
Budget Amount *help
¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000)
Fiscal Year 2024: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2023: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2022: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Keywordsレドックス / ニトロキシルラジカル / NMR / 腫瘍 / メタボロミクス / 高磁場NMR / DNP / 超偏極 / 癌
Outline of Research at the Start

本研究では非侵襲的に腫瘍のレドックス代謝を可視化する超偏極MRI/CmP技術と800MHz高磁場NMRを用いたプローブ代謝および腫瘍内レドックス分子に特化したレドックスメタボロミクスを構築し、生体計測での腫瘍内レドックス変動分子のメカニズム解明を目的とする。

Outline of Final Research Achievements

In this study, we aimed to achieve a comprehensive visualization of cancer pathology by combining in vivo redox imaging using dynamic nuclear polarization MRI (DNP-MRI) with high-field NMR-based metabolomic analysis for the detection of disease-related metabolites.Focusing on the tumor microenvironment, where imbalances in oxidative stress and antioxidant mechanisms play a critical role, we established a tumor-bearing mouse model and performed redox imaging. In parallel, we investigated metabolomic profiling of redox-related molecules.
For visualizing redox status, we successfully imaged the redox state in a pancreatic cancer xenograft model using carbamoyl-PROXYL. Additionally, high-field NMR-based metabolomics revealed that several redox-related compounds such as NADH and GSH could be detected with high sensitivity.

Academic Significance and Societal Importance of the Research Achievements

がんの早期発見や治療効果の迅速な判定が可能となり、患者ごとの病態に応じた個別化医療(プレシジョンメディシン)の実現に寄与するとともに、不要な治療の回避や予後の改善に貢献する。また、画像診断と分子レベルの代謝情報を統合的に解析する本手法は、従来の形態中心の診断を超えた新たな診断パラダイムを提示しうる。さらに、本研究で得られる知見は、がんのみならず、他の酸化ストレス関連疾患への応用可能性も秘めており、広範な医学分野における診断・治療戦略の革新につながる社会的意義が極めて大きい。

Report

(4 results)
  • 2024 Annual Research Report   Final Research Report ( PDF )
  • 2023 Research-status Report
  • 2022 Research-status Report
  • Research Products

    (5 results)

All 2024 2022

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

  • [Journal Article] Quantitative spatial visualization of X-ray irradiation via redox reaction by dynamic nuclear polarization magnetic resonance imaging2024

    • Author(s)
      Koyasu Norikazu、Hyodo Fuminori、Iwasaki Ryota、Elhelaly Abdelazim Elsayed、Mori Takashi、Noda Yoshifumi、Kato Hiroki、Krishna Murali C.、Kishimoto Shun、Matsuo Masayuki
    • Journal Title

      Free Radical Biology and Medicine

      Volume: 225 Pages: 388-397

    • DOI

      10.1016/j.freeradbiomed.2024.10.278

    • Related Report
      2024 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Continuous monitoring of postirradiation reoxygenation and cycling hypoxia using electron paramagnetic resonance imaging2022

    • Author(s)
      Kawai Tatsuya、Matsuo Masayuki、Takakusagi Yoichi、Saito Keita、Hyodo Fuminori、Devasahayam Nallathamby、Matsumoto Shingo、Kishimoto Shun、Yasui Hironobu、Yamamoto Kazutoshi、Krishna Murali C.
    • Journal Title

      NMR in Biomedicine

      Volume: 35 Issue: 10 Pages: 4783-4783

    • DOI

      10.1002/nbm.4783

    • Related Report
      2022 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Noninvasive Diagnosis of the Mitochondrial Function of Doxorubicin-Induced Cardiomyopathy Using In Vivo Dynamic Nuclear Polarization?Magnetic Resonance Imaging2022

    • Author(s)
      Mizuta Yukie、Akahoshi Tomohiko、Eto Hinako、Hyodo Fuminori、Murata Masaharu、Tokuda Kentaro、Eto Masatoshi、Yamaura Ken
    • Journal Title

      Antioxidants

      Volume: 11 Issue: 8 Pages: 1454-1454

    • DOI

      10.3390/antiox11081454

    • Related Report
      2022 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Presentation] Application of Hyperpolarized 13C Pyruvate Magnetic Resonance Spectroscopy for Monitoring Epilepsy2022

    • Author(s)
      Abdelazim Elsayed Elhelaly, Fuminori Hyodo, Norikazu Koyasu, Masayuki Matsuo
    • Organizer
      第50回日本磁気共鳴医学会大会
    • Related Report
      2022 Research-status Report
  • [Presentation] Usage of Dissolution Dynamic Nuclear Polarization Magnetic Resonance Spectroscopy Depicts Efficacy of Chemotherapeutic and Radiotherapeutic anticancer interferences2022

    • Author(s)
      Abdelazim Elsayed Elhelaly, Fuminori Hyodo, Norikazu Koyasu, Hiroyuki Tomita, Masaharu Murata, Yoshifumi Noda, Hiroki Kato, Masayuki Matsuo
    • Organizer
      Joint Annual Meeting ISMRM-ESMRMB & ISMRT 31st Annual Meeting
    • Related Report
      2022 Research-status Report

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Published: 2022-04-19   Modified: 2026-01-16  

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