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Development of novel PET ligands for p62/SQSTM1

Research Project

Project/Area Number 16K19872
Research Category

Grant-in-Aid for Young Scientists (B)

Allocation TypeMulti-year Fund
Research Field Radiation science
Research InstitutionNational Institutes for Quantum and Radiological Science and Technology

Principal Investigator

Ono Maiko  国立研究開発法人量子科学技術研究開発機構, 放射線医学総合研究所 脳機能イメージング研究部, 研究員(任常) (70595876)

Project Period (FY) 2016-04-01 – 2019-03-31
Project Status Completed (Fiscal Year 2018)
Budget Amount *help
¥3,770,000 (Direct Cost: ¥2,900,000、Indirect Cost: ¥870,000)
Fiscal Year 2018: ¥650,000 (Direct Cost: ¥500,000、Indirect Cost: ¥150,000)
Fiscal Year 2017: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2016: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Keywordsポジトロン断層撮影(PET) / イメージング / オートファジー / p62 / 神経変性疾患 / 疾患マーカー / PETイメージング / 脳神経疾患 / 放射線 / トランスレーショナルリサーチ
Outline of Final Research Achievements

p62/SQSTM1 is a substrate for selective autophary, and colocalized with abnormal protein aggregates formed in the brain of various neurodegenerative disease. In vivo imaging technology for visualization of p62 accumulation in the living brain provide cross-pathological markers of neurodegenerative disease. In this study, we developed a novel positron emission tomography (PET) imaging ligands for p62. Two of our candidate compounds were confirmed to bind to p62 in biomolecular interaction analysis and a cultured cell-based assay, respectively. Further, one candidate showed accumulation at abnormal protein aggregates in the brain of neurodegenerative disease mouse model, suggesting that this candidate also binds to p62 in vivo. Further investigations of those candidate compounds found in this study will contribute to the creation of useful p62 PET imaging agents.

Academic Significance and Societal Importance of the Research Achievements

本研究で見いだされたp62 PETプローブ候補化合物は、p62の蓄積を生体内で画像化する分子イメージング技術の創製に寄与し得る。開発を行ったPETプローブはヒトでの応用が可能であり、様々な神経変性疾患の疾患横断的スクリーニングを可能にする新たなツールへの発展が期待される。

Report

(2 results)
  • 2018 Annual Research Report   Final Research Report ( PDF )
  • Research Products

    (11 results)

All 2019 2018 Other

All Int'l Joint Research (3 results) Journal Article (4 results) (of which Int'l Joint Research: 3 results,  Peer Reviewed: 4 results,  Open Access: 4 results) Presentation (3 results) (of which Int'l Joint Research: 1 results,  Invited: 2 results) Remarks (1 results)

  • [Int'l Joint Research] Mayo Clinic/University of Pennsylvania(米国)

    • Related Report
      2018 Annual Research Report
  • [Int'l Joint Research] Karolinska Institutet(スウェーデン)

    • Related Report
      2018 Annual Research Report
  • [Int'l Joint Research] Erasmus Medical Center(オランダ)

    • Related Report
      2018 Annual Research Report
  • [Journal Article] In vivo binding of a tau imaging probe, [ 11 C]PBB3, in patients with progressive supranuclear palsy2019

    • Author(s)
      Endo Hironobu、Shimada Hitoshi、Sahara Naruhiko、Ono Maiko、Koga Shunsuke、Kitamura Soichiro、Niwa Fumitoshi、Hirano Shigeki、Kimura Yasuyuki、Ichise Masanori、Shinotoh Hitoshi、Zhang Ming Rong、Kuwabara Satoshi、Dickson Dennis W.、Toda Tatsushi、Suhara Tetsuya、Higuchi Makoto
    • Journal Title

      Movement Disorders

      Volume: 34 Issue: 5 Pages: 744-754

    • DOI

      10.1002/mds.27643

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Tau imaging detects distinctive distribution of tau pathology in ALS/PDC on the Kii Peninsula2018

    • Author(s)
      Shinotoh Hitoshi、Shimada Hitoshi、Kokubo Yasumasa、Tagai Kenji、Niwa Fumitoshi、Kitamura Soichiro、Endo Hironobu、Ono Maiko、Kimura Yasuyuki、Hirano Shigeki、Mimuro Maya、Ichise Masanori、Sahara Naruhiko、Zhang Ming-Rong、Suhara Tetsuya、Higuchi Makoto
    • Journal Title

      Neurology

      Volume: 92 Issue: 2

    • DOI

      10.1212/wnl.0000000000006736

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Comparative in-vitro quantification of pathological tau deposits and their association with neurodegeneration in tauopathy mouse models2018

    • Author(s)
      Ni R, Ji B, Ono M, Sahara N, Zhang M-R, Aoki I, Nordberg A, Suhara T, Higuchi M
    • Journal Title

      J. Nuclear Medicine

      Volume: 117 Issue: 6 Pages: 960-966

    • DOI

      10.2967/jnumed.117.201632

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] In Vivo Visualization of Tau Accumulation, Microglial Activation, and Brain Atrophy in a Mouse Model of Tauopathy rTg45102018

    • Author(s)
      Ishikawa Ai、Tokunaga Masaki、Maeda Jun、Minamihisamatsu Takeharu、Shimojo Masafumi、Takuwa Hiroyuki、Ono Maiko、Ni Ruiqing、Hirano Shigeki、Kuwabara Satoshi、Ji Bin、Zhang Ming-Rong、Aoki Ichio、Suhara Tetsuya、Higuchi Makoto、Sahara Naruhiko
    • Journal Title

      Journal of Alzheimer's Disease

      Volume: 61 Issue: 3 Pages: 1037-1052

    • DOI

      10.3233/jad-170509

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Presentation] タウから見たアルツハイマー病の診断から治療の可能性2018

    • Author(s)
      小野麻衣子
    • Organizer
      第41回日本分子生物学会年会
    • Related Report
      2018 Annual Research Report
    • Invited
  • [Presentation] 認知症疾患のタウ病理とイメージング2018

    • Author(s)
      小野麻衣子
    • Organizer
      第37回日本認知症学会学術集会
    • Related Report
      2018 Annual Research Report
    • Invited
  • [Presentation] Development of a tau PET ligand, [18F]PM-PBB32018

    • Author(s)
      Maiko Ono, Hitoshi Shimada, Soichiro Kitamura, Kenji Tagai, Manabu Kubota, Hiroyuki Takuwa, Paul Tempest, Ming-Kuei Jang, John Seibyl, Olivier Barret, David Alagille, Kenneth Marek, Naruhiko Sahara, Tetsuya Suhara, Ming-Rong Zhang, and Makoto Higuchi
    • Organizer
      AAT-AD/PD Focus Meeting 2018
    • Related Report
      2018 Annual Research Report
    • Int'l Joint Research
  • [Remarks] 脳機能イメージング研究部

    • URL

      http://www.nirs.qst.go.jp/seika/brain/

    • Related Report
      2018 Annual Research Report

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

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