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Search of conformation-specific PET probe

Research Project

Project/Area Number 16K15570
Research Category

Grant-in-Aid for Challenging Exploratory Research

Allocation TypeMulti-year Fund
Research Field Radiation science
Research InstitutionTohoku Medical and Pharmaceutical University

Principal Investigator

OKAMURA Nobuyuki  東北医科薬科大学, 医学部, 教授 (40361076)

Project Period (FY) 2016-04-01 – 2019-03-31
Project Status Completed (Fiscal Year 2018)
Budget Amount *help
¥3,510,000 (Direct Cost: ¥2,700,000、Indirect Cost: ¥810,000)
Fiscal Year 2018: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2017: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2016: ¥650,000 (Direct Cost: ¥500,000、Indirect Cost: ¥150,000)
Keywords分子イメージング / αシヌクレイン / PET / イメージング / PETプローブ / 脳神経疾患 / 痴呆 / 放射線
Outline of Final Research Achievements

To develop a PET probe for in vivo monitoring of misfolded protein accumulation, we tested the binding and pharmacokinetic properties of our library compounds and found a series of novel compound that can clearly stain Lewy bodies. A candidate compound (Cpd.365) showed excellent blood-brain barrier permeability in mice. Autoradiography using postmortem human brain samples showed strong binding of 18F-labeled compound to α-synuclein rich brain sections, although the binding selectivity of this compound was insufficient for selective α-synuclein probe.

Academic Significance and Societal Importance of the Research Achievements

プローブが実用化され、パーキンソン病などのミスフォールディングの脳内蓄積を生体で非侵襲的に計測できれば、多様な神経変性疾患の早期診断のためのスクリーニング法となる。また新たな治療評価系としても活用でき新規治療薬開発と連動させるによって疾患の撲滅へ向けた第一歩となる。

Report

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

    (24 results)

All 2018 2017 2016

All Journal Article (17 results) (of which Int'l Joint Research: 7 results,  Peer Reviewed: 16 results,  Open Access: 9 results,  Acknowledgement Compliant: 2 results) Presentation (6 results) (of which Int'l Joint Research: 2 results,  Invited: 5 results) Book (1 results)

  • [Journal Article] Imaging Protein Misfolding in the Brain Using β-Sheet Ligands2018

    • Author(s)
      Harada Ryuichi、Okamura Nobuyuki、Furumoto Shozo、Yanai Kazuhiko
    • Journal Title

      Frontiers in Neuroscience

      Volume: 12 Pages: 585-585

    • DOI

      10.3389/fnins.2018.00585

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] [18F]THK-5351 PET imaging in early-stage semantic variant primary progressive aphasia: a report of two cases and a literature review2018

    • Author(s)
      Kobayashi Ryota、Hayashi Hiroshi、Kawakatsu Shinobu、Ishiki Aiko、Okamura Nobuyuki、Arai Hiroyuki、Otani Koichi
    • Journal Title

      BMC Neurology

      Volume: 18 Issue: 1 Pages: 109-109

    • DOI

      10.1186/s12883-018-1115-3

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Neuroimaging-pathological correlations of [(18)F]THK5351 PET in progressive supranuclear palsy2018

    • Author(s)
      Ishiki A, Furukawa K, et al.
    • Journal Title

      Acta Neuropathol Commun

      Volume: 6 Issue: 1 Pages: 53-53

    • DOI

      10.1186/s40478-018-0556-7

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] THK5351-PETから見えてきた分子イメージングの新しい方向性2018

    • Author(s)
      岡村信行、原田龍一、江面道典、工藤幸司
    • Journal Title

      日本認知症学会誌

      Volume: 32 Pages: 538-545

    • Related Report
      2018 Annual Research Report
  • [Journal Article] [18F]-THK5351 PET correlates with topology and symptom severity in progressive supranuclear palsy.2018

    • Author(s)
      Brendel M, Schoneckerr S, Hoglinger G, Lindner S, Havla J, Blautzik J, Sauerbeck J, Rohrer G, Zach C, Vettermann F, Lang AE, Golbe L, Nubling G, Bartenstein P, Furukawa K, Ishiki A, Botzel K, Danek A, Okamura N, Levin J, Rominger A.
    • Journal Title

      Front Aging Neurosci.

      Volume: 9 Pages: 440-440

    • DOI

      10.3389/fnagi.2017.00440

    • Related Report
      2017 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Correlations of (18)F-THK5351 PET with Postmortem Burden of Tau and Astrogliosis in Alzheimer Disease.2018

    • Author(s)
      Harada R, Furukawa K, et al.
    • Journal Title

      J Nucl Med

      Volume: 59 Issue: 4 Pages: 671-674

    • DOI

      10.2967/jnumed.117.197426

    • Related Report
      2017 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Comparative binding properties of the tau PET tracers THK5117, THK5351, PBB3, and T807 in postmortem Alzheimer brains.2017

    • Author(s)
      Lemoine L, Gillberg PG, Svedberg M, Stepanov V, Jia Z, Huang J, Nag S, Tian H, Ghetti B, Okamura N, Higuchi M, Halldin C, Nordberg A.
    • Journal Title

      Alzheimers Res Ther.

      Volume: 9 Issue: 1 Pages: 96-96

    • DOI

      10.1186/s13195-017-0325-z

    • Related Report
      2017 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] アルツハイマー病理を標的とした分子イメージングプローブの開発2017

    • Author(s)
      岡村信行、原田龍一、古本祥三、中村正帆、谷内一彦,工藤幸司
    • Journal Title

      日本薬理学雑誌

      Volume: 150 Pages: 172-176

    • NAID

      130006107929

    • Related Report
      2017 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] 18F-Labeled 2-Arylquinoline Derivatives for Tau Imaging: Chemical, Radiochemical, Biological and Clinical Features.2017

    • Author(s)
      Furumoto S, Tago T, Harada R, Kudo Y, Okamura N.
    • Journal Title

      Curr Alzheimer Res.

      Volume: 14 Pages: 178-185

    • Related Report
      2016 Research-status Report
    • Peer Reviewed
  • [Journal Article] Structure-Activity Relationship of 2-Arylquinolines as PET Imaging Tracers for Tau Pathology in Alzheimer’s Disease2016

    • Author(s)
      Tetsuro Tago, Shozo Furumoto, Nobuyuki Okamura, Ryuichi Harada, Hajime Adachi, Yoichi Ishikawa, Kazuhiko Yanai, Ren Iwata, and Yukitsuka Kudo
    • Journal Title

      Journal of Nuclear Medicine

      Volume: 57(4) Issue: 4 Pages: 608-614

    • DOI

      10.2967/jnumed.115.166652

    • Related Report
      2016 Research-status Report
    • Peer Reviewed
  • [Journal Article] Advances in the development of tau PET radiotracers and their clinical applications.2016

    • Author(s)
      Okamura N, Harada R, Furukawa K, Furumoto S, Tago T, Yanai K, Arai H, Kudo Y.
    • Journal Title

      Ageing Res Rev.

      Volume: - Pages: 107-113

    • DOI

      10.1016/j.arr.2015.12.010

    • Related Report
      2016 Research-status Report
    • Peer Reviewed
  • [Journal Article] microPET Imaging of Tau Pathology with [18F]-THK5117 in two Transgenic Mouse Models.2016

    • Author(s)
      Brendel M, Jaworska A, Probst F, Overhoff F, Korzhova V, Lindner S, Carlsen J, Bartenstein P, Harada R, Kudo Y, Haass C, van Leuven F, Okamura N, Herms J, Rominger A.
    • Journal Title

      J Nucl Med

      Volume: 印刷中 Issue: 5 Pages: 792-798

    • DOI

      10.2967/jnumed.115.163493

    • Related Report
      2016 Research-status Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] Introduction and overview of the special issue "Brain imaging and aging": The new era of neuroimaging in aging research.2016

    • Author(s)
      Furukawa K, Ishiki A, Tomita N, Onaka Y, Saito H, Nakamichi T, Hara K, Kusano Y, Ebara M, Arata Y, Sakota M, Miyazawa I, Totsune T, Okinaga S, Okamura N, Kudo Y, Arai H.
    • Journal Title

      Ageing Res Rev

      Volume: - Pages: 1-3

    • DOI

      10.1016/j.arr.2016.02.005

    • Related Report
      2016 Research-status Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [Journal Article] Dynamic PET measures of tau accumulation in cognitively normal older adults and Alzheimer's disease patients measured using [18F]THK-5351.2016

    • Author(s)
      Lockhart SN, Baker SL, Okamura N, Furukawa K, Ishiki A, Furumoto S, Tashiro M, Yanai K, Arai H, Kudo Y, Harada R, Tomita N, Hiraoka K, Watanuki S, Jagust WJ.
    • Journal Title

      PLoS One.

      Volume: 11 Issue: 6 Pages: e0158460-e0158460

    • DOI

      10.1371/journal.pone.0158460

    • Related Report
      2016 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Characterization of the radiolabeled metabolite of tau PET tracer 18F-THK5351.2016

    • Author(s)
      Harada R, Furumoto S, Tago T, Furukawa K, Ishiki A, Tomita N, Iwata R, Tashiro M, Arai H, Yanai K, Kudo Y, Okamura N.
    • Journal Title

      Eur J Nucl Med Mol Imaging.

      Volume: 43 Issue: 12 Pages: 2211-2218

    • DOI

      10.1007/s00259-016-3453-y

    • Related Report
      2016 Research-status Report
    • Peer Reviewed / Acknowledgement Compliant
  • [Journal Article] Untangling tau imaging.2016

    • Author(s)
      Villemagne VL, Okamura N, Rowe CC.
    • Journal Title

      Alzheimers Dement (Amst)

      Volume: 4 Issue: 1 Pages: 39-42

    • DOI

      10.1016/j.dadm.2016.05.001

    • Related Report
      2016 Research-status Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] In vivo visualization of tau pathology using 18F-THK5351 PET in corticobasal syndrome.2016

    • Author(s)
      Kikuchi A, Okamura N, Hasegawa T, Harada R, Watanuki S, Funaki Y, Kobayashi M, Tano O, Baba T, Sugeno N, Oshima R, Yoshida S, Kobayashi J, Ezura M, Hiraoka K, Mugikura S, Takase K, Iwata R, Taki Y, Furukawa K, HArai H, Furumoto S, Tashiro M, Yanai K, Kudo Y, Takeda A,Aoki M.
    • Journal Title

      Neurology

      Volume: 87 Issue: 22 Pages: 2309-2316

    • DOI

      10.1212/wnl.0000000000003375

    • Related Report
      2016 Research-status Report
    • Peer Reviewed
  • [Presentation] Toward the development of novel imaging agents for protein misfolding diseases.2018

    • Author(s)
      Okamura N.
    • Organizer
      2018 International Conference on Neurodegenerative Disorders, CGMH
    • Related Report
      2018 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] 認知症の画像診断の最先端2018

    • Author(s)
      岡村信行、原田龍一
    • Organizer
      第33回日本老年精神医学会
    • Related Report
      2018 Annual Research Report
    • Invited
  • [Presentation] Development of PET tracers for imaging amyloid, tau and gliosis.2018

    • Author(s)
      岡村信行、原田龍一
    • Organizer
      第58回日本核医学会学術集会
    • Related Report
      2018 Annual Research Report
    • Invited
  • [Presentation] Novel tracer development and potential application for movement disorders.2017

    • Author(s)
      Okamura N.
    • Organizer
      3rd Taiwan International Congress of Parkinson's Disease and Movement Disorders
    • Place of Presentation
      台北(台湾)
    • Year and Date
      2017-03-19
    • Related Report
      2016 Research-status Report
    • Int'l Joint Research / Invited
  • [Presentation] 認知症を標的とした分子イメージングプローブ開発の現状2017

    • Author(s)
      岡村信行
    • Organizer
      第32回日本老年精神医学会
    • Related Report
      2017 Research-status Report
    • Invited
  • [Presentation] 認知症を標的とした分子イメージングプローブ開発の現状2017

    • Author(s)
      岡村信行
    • Organizer
      第60回日本脳循環代謝学会学術集会
    • Related Report
      2017 Research-status Report
  • [Book] Neuroimaging Diagnosis for Alzheimer’s Disease and Other Dementias.2017

    • Author(s)
      Okamura N.
    • Total Pages
      279
    • Publisher
      Springer
    • ISBN
      9784431551331
    • Related Report
      2017 Research-status Report

URL: 

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

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