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PET imaging for oxidative stress in patients with Alzheimer's disease

Research Project

Project/Area Number 16K09712
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Research Field Neurology
Research InstitutionUniversity of Fukui

Principal Investigator

Ikawa Masamichi  福井大学, 学術研究院医学系部門, 講師 (60444212)

Co-Investigator(Kenkyū-buntansha) 岡沢 秀彦  福井大学, 高エネルギー医学研究センター, 教授 (50360813)
米田 誠  福井県立大学, 看護福祉学部, 教授 (70270551)
Project Period (FY) 2016-04-01 – 2019-03-31
Project Status Completed (Fiscal Year 2018)
Budget Amount *help
¥4,680,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥1,080,000)
Fiscal Year 2018: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2017: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000)
Fiscal Year 2016: ¥2,340,000 (Direct Cost: ¥1,800,000、Indirect Cost: ¥540,000)
Keywordsアルツハイマー病 / 酸化ストレス / PETイメージング / 認知症 / 脳神経疾患 / 痴呆 / 放射線
Outline of Final Research Achievements

Oxidative stress is assumed to be the pathogenic mechanisms underlying Alzheimer's disease (AD). In this study, we applied [Cu-64]ATSM PET/MRI to image cerebral oxidative stress in living patients with AD. PET imaging successfully demonstrated the increased uptake in brain patients with AD. The uptake correlated with disease severity, indicating that oxidative stress is associated with the neurodegenerative process in AD. [Cu-64]ATSM PET/MRI imaging for oxidative stress has improved our insights into the pathological mechanisms of neurodegenerative diseases including AD and may be a promising tool for monitoring further antioxidant therapies.

Academic Significance and Societal Importance of the Research Achievements

本研究では,これまで基礎研究やモデル動物のみで示されていた,アルツハイマー病(AD)の病態における酸化ストレス増強を,実際の患者生体で明らかにすることができた点に大きな学術的意義がある.本研究の成果によって,[Cu-64]ATSM PET/MRIの酸化ストレスイメージングとしての有用性が示され,さらに酸化ストレスの抑制がADに対して有効である可能性が示唆された.ADに対する予防・予測および創薬につながる成果であると考えられる.

Report

(4 results)
  • 2018 Annual Research Report   Final Research Report ( PDF )
  • 2017 Research-status Report
  • 2016 Research-status Report
  • Research Products

    (27 results)

All 2019 2018 2017 2016

All Journal Article (11 results) (of which Int'l Joint Research: 5 results,  Peer Reviewed: 8 results,  Open Access: 3 results,  Acknowledgement Compliant: 1 results) Presentation (12 results) (of which Int'l Joint Research: 6 results,  Invited: 3 results) Book (4 results)

  • [Journal Article] 酸化ストレスイメージング-ミトコンドリア病,神経変性疾患への応用2019

    • Author(s)
      井川 正道, 岡沢 秀彦, 米田 誠
    • Journal Title

      BRAIN and NERVE-神経研究の進歩

      Volume: 71 Pages: 161-166

    • NAID

      40021795245

    • Related Report
      2018 Annual Research Report
  • [Journal Article] Arterial spin labeling MR imaging for the clinical detection of cerebellar hypoperfusion in patients with spinocerebellar degeneration.2018

    • Author(s)
      Ikawa M, Kimura, H, Kitazaki Y, Sugimoto K, Matsunaga A, Hayashi K, Yamamura O, Tsujikawa T, Hamano T, Yoneda M, Okazawa H, Nakamoto Y.
    • Journal Title

      J Neurol Sci

      Volume: 394 Pages: 58-62

    • DOI

      10.1016/j.jns.2018.09.007

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed
  • [Journal Article] 3-Substituted 1,5-Diaryl-1H-1,2,4-triazoles as Prospective PET Radioligands for Imaging Brain COX-1 in Monkey. Part 2: Selection and Evaluation of [11C]PS13 for Quantitative Imaging2018

    • Author(s)
      Shrestha Stal、Singh Prachi、Cortes-Salva Michelle Y.、Jenko Kimberly J.、Ikawa Masamichi、Kim Min-Jeong、Kobayashi Masato、Morse Cheryl L.、Gladding Robert L.、Liow Jeih-San、Zoghbi Sami S.、Fujita Masahiro、Innis Robert B.、Pike Victor W.
    • Journal Title

      ACS Chemical Neuroscience

      Volume: 9 Issue: 11 Pages: 2620-2627

    • DOI

      10.1021/acschemneuro.8b00103

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] ミトコンドリア病の病態メカニズム2018

    • Author(s)
      井川 正道, 米田 誠
    • Journal Title

      Medical Science Digest

      Volume: 44 Pages: 559-562

    • Related Report
      2018 Annual Research Report
  • [Journal Article] Comparison of four 11C-labeled PET ligands to quantify translocator protein 18?kDa (TSPO) in human brain: (R)-PK11195, PBR28, DPA-713, and ER176?based on recent publications that measured specific-to-non-displaceable ratios2017

    • Author(s)
      Fujita M, Kobayashi M, Ikawa M, Gunn RN,, Rabiner EA, Owen DR, Zoghbi SS, Haskali MB, Telu S, Pike VW, Innis RB
    • Journal Title

      EJNMMI Research

      Volume: 7 Issue: 1 Pages: 84-84

    • DOI

      10.1186/s13550-017-0334-8

    • Related Report
      2017 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Precise Evaluation of Striatal Oxidative Stress Corrected for Severity of Dopaminergic Neuronal Degeneration in Patients with Parkinson’s Disease: A Study with <sup>62</sup>Cu-ATSM PET and <sup>123</sup>I-FP-CIT SPECT2017

    • Author(s)
      Neishi H, Ikawa M, Okazawa H, Tsujikawa T, Arishima H, Kikuta KI, Yoneda M
    • Journal Title

      European Neurology

      Volume: 78 Issue: 3-4 Pages: 161-168

    • DOI

      10.1159/000479627

    • Related Report
      2017 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] ミトコンドリア病2017

    • Author(s)
      井川 正道、米田 誠
    • Journal Title

      日本内科学会誌

      Volume: 106 Pages: 1584-1590

    • Related Report
      2017 Research-status Report
    • Peer Reviewed
  • [Journal Article] 11C-ER176, a Radioligand for 18-kDa Translocator Protein, Has Adequate Sensitivity to Robustly Image All Three Affinity Genotypes in Human Brain2017

    • Author(s)
      Ikawa M, Lohith TG, Shrestha S, Telu S, Zoghbi SS, Castellano S, Taliani S, Da Settimo F, Fujita M, Pike VW, Innis RB; Biomarkers Consortium Radioligand Project Team
    • Journal Title

      J Nucl Med

      Volume: 58 Issue: 2 Pages: 320-325

    • DOI

      10.2967/jnumed.116.178996

    • Related Report
      2016 Research-status Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] Limbic encephalitis associated with anti-NH2-terminal of α-enolase antibodies: A clinical subtype of Hashimoto encephalopathy.2017

    • Author(s)
      Kishitani T, Matsunaga A, Ikawa M, Hayashi K, Yamamura O, Hamano T, Watanabe O, Tanaka K, Nakamoto Y, Yoneda M
    • Journal Title

      Medicine

      Volume: 96(10) Issue: 10 Pages: e6181-e6181

    • DOI

      10.1097/md.0000000000006181

    • Related Report
      2016 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
  • [Journal Article] ミトコンドリア代謝・酸化ストレスの分子イメージング2017

    • Author(s)
      井川 正道, 米田 誠
    • Journal Title

      医学のあゆみ

      Volume: 60 Pages: 67-72

    • Related Report
      2016 Research-status Report
  • [Journal Article] The 5-HT1A receptor PET radioligand 11C-CUMI-101 has significant binding to α1adrenoceptors in human cerebellum, limiting its use as a reference region2016

    • Author(s)
      Shrestha SS, Liow JS, Jenko K, Ikawa M, Zoghbi SS, Innis RB
    • Journal Title

      J Nucl Med

      Volume: 57 Pages: 1945-1948

    • Related Report
      2016 Research-status Report
    • Peer Reviewed / Int'l Joint Research
  • [Presentation] Feasibility of Arterial Spin Labeling MR Imaging for Detecting Cerebellar Hypoperfusion in Patients with Spinocerebellar Degeneration2018

    • Author(s)
      Masamichi Ikawa, Hirohiko Kimura, Yuki Kitazaki, Akiko Matsunaga, Koji Hayashi, Osamu Yamamura, Tadanori Hamano, Makoto Yoneda, Hidehiko Okazawa, Yasunari Nakamoto
    • Organizer
      American Academy of Neurology 2018
    • Related Report
      2018 Annual Research Report
    • Int'l Joint Research
  • [Presentation] PET neuroimaging for oxidative stress based on mitochondrial dysfunction in patients with neurodegenerative diseases2018

    • Author(s)
      Masamichi Ikawa, Hidehiko Okazawa, Tetsuya Tsujikawa, Osamu Yamamura, Tadanori Hamano, Yasunari Nakamoto, Makoto Yoneda
    • Organizer
      Asian Society for Mitochondrial Research and Medicine 2018
    • Related Report
      2018 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Clinical application of arterial spin labeling MRI in patients with spinocerebellar degeneration2018

    • Author(s)
      井川 正道, 木村 浩彦, 北崎 佑樹, 松永 晶子, 林 浩嗣, 山村 修, 濱野 忠則, 米田 誠, 岡沢 秀彦, 中本 安成
    • Organizer
      第59回日本神経学会学術集会
    • Related Report
      2018 Annual Research Report
  • [Presentation] 神経変性疾患の酸化ストレスPETイメージング2018

    • Author(s)
      井川 正道
    • Organizer
      第61回日本脳循環代謝学会学術集会
    • Related Report
      2018 Annual Research Report
    • Invited
  • [Presentation] Dopaminergic neuronal oxidative stress is increased with disease severity in patients with Parkinson's disease: A study with PET and SPECT2017

    • Author(s)
      Ikawa M, Okazawa H, Neishi H, Tsujikawa T, Kikuta K, Nakamoto Y, Yoneda M
    • Organizer
      13th Conference on Quantification of Brain Function with PET
    • Related Report
      2017 Research-status Report
    • Int'l Joint Research
  • [Presentation] Dopaminergic neuronal oxidative stress is increased with disease progression in patients with Parkinson’s disease: A study with PET and SPECT2017

    • Author(s)
      Ikawa M, Okazawa H, Neishi H, Kitazaki Y, Tsujikawa T, Kikuta K, Nakamoto Y, Yoneda M
    • Organizer
      The 69th Annual Meeting of American Academy of Neurology
    • Related Report
      2017 Research-status Report
    • Int'l Joint Research
  • [Presentation] PET neuroimaging for oxidative stress based on mitochondrial dysfunction in neurodegenerative diseases2017

    • Author(s)
      Ikawa M, Okazawa H, Tsujikawa T, Nakamoto Y, Yoneda M
    • Organizer
      The XXIII World Congress of Neurology
    • Related Report
      2017 Research-status Report
    • Int'l Joint Research
  • [Presentation] ミトコンドリア病のイメージング2017

    • Author(s)
      井川 正道
    • Organizer
      第17回日本ミトコンドリア学会年会
    • Related Report
      2017 Research-status Report
    • Invited
  • [Presentation] アルツハイマー病患者における64Cu-ATSM PET/MR酸化ストレスイメージング2017

    • Author(s)
      井川 正道, 岡沢 秀彦, 辻川 哲也, 森 哲也, 清野 泰, 米田 誠
    • Organizer
      第57回日本核医学会学術総会
    • Related Report
      2017 Research-status Report
  • [Presentation] 分子イメ ージングによるMELAS脳卒中様発作の病態解明2017

    • Author(s)
      井川 正道, 岡沢 秀彦, 辻川 哲也, 清野 智恵子, 前田 浩幸, 川谷 正男, 畑 郁江, 木村 浩彦, 米田 誠
    • Organizer
      日本人類遺伝学会第62回大会
    • Related Report
      2017 Research-status Report
  • [Presentation] Molecular Imaging for Mitochondrial Diseases2016

    • Author(s)
      Ikawa M, Yoneda M
    • Organizer
      13th ASMRM & 16th J-mit
    • Place of Presentation
      TKPガーデンシティ品川(東京都品川区)
    • Year and Date
      2016-11-01
    • Related Report
      2016 Research-status Report
    • Int'l Joint Research / Invited
  • [Presentation] Evaluation of cerebral oxidative stress in patients with ALS using 62Cu-ATSM PET2016

    • Author(s)
      Ikawa M, Okazawa H, Tsujikawa T, Matsunaga A, Yamamura O, Mori T, Hamano T, Kiyono Y, Nakamoto Y, Yoneda M
    • Organizer
      第57回日本神経学会学術大会
    • Place of Presentation
      神戸コンベンションセンター(兵庫県神戸市)
    • Year and Date
      2016-05-18
    • Related Report
      2016 Research-status Report
  • [Book] 希少疾患用医薬品の適応拡大と事業性評価2018

    • Author(s)
      井川 正道, 米田 誠
    • Total Pages
      538
    • Publisher
      技術情報協会
    • ISBN
      9784861047268
    • Related Report
      2018 Annual Research Report
  • [Book] 別冊・医学のあゆみ2017

    • Author(s)
      井川 正道, 米田 誠
    • Total Pages
      6
    • Publisher
      医歯薬出版
    • Related Report
      2017 Research-status Report
  • [Book] Annual Review神経 20172017

    • Author(s)
      井川 正道, 岡沢 秀彦, 米田 誠
    • Total Pages
      7
    • Publisher
      中外医学社
    • Related Report
      2016 Research-status Report
  • [Book] 脳内環境辞典2017

    • Author(s)
      米田 誠, 井川 正道, 岡沢 秀彦
    • Total Pages
      2
    • Publisher
      メディカルドゥ
    • Related Report
      2016 Research-status Report

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Published: 2016-04-21   Modified: 2020-03-30  

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