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Comparative study of tau imaging tracers

Research Project

Project/Area Number 15K19767
Research Category

Grant-in-Aid for Young Scientists (B)

Allocation TypeMulti-year Fund
Research Field Radiation science
Research InstitutionTohoku University

Principal Investigator

Ryuichi Harada  東北大学, 医学系研究科, 助教 (60735455)

Project Period (FY) 2015-04-01 – 2017-03-31
Project Status Completed (Fiscal Year 2016)
Budget Amount *help
¥3,900,000 (Direct Cost: ¥3,000,000、Indirect Cost: ¥900,000)
Fiscal Year 2016: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2015: ¥2,340,000 (Direct Cost: ¥1,800,000、Indirect Cost: ¥540,000)
Keywords放射性医薬品 / 造影剤 / イメージング / 神経変性疾患 / 神経機能画像 / 放射性医薬品・造影剤 / 神経機能画像学
Outline of Final Research Achievements

In this study, we characterized the binding and pharmacokinetic profiles of 18F-THK5351 we developed and other reported tracer 18F-AV1451. In 18F-THK5351, radiolabeled sulfoconjugate was observed in mice and human as dominant metabolite and it showed little brain uptake, indicating its radiolabeled metabolite does not affect PET images of 18F-THK5351 in human. In addition, we found off-target binding of 18F-THK5351 was monoamine oxidase-B (MAO-B). These results suggest that 18F-THK5351 PET signal reflects tau as well as MAO-B binding. On the other hand, other off-target binding substrates of 18F-AV1451 were present, although MAO-A and melanin have been already reported. This study highlights the need for the consideration of further validation to better understand PET images using tau PET radiotracers.

Report

(3 results)
  • 2016 Annual Research Report   Final Research Report ( PDF )
  • 2015 Research-status Report
  • Research Products

    (26 results)

All 2017 2016 2015 Other

All Int'l Joint Research (2 results) Journal Article (13 results) (of which Int'l Joint Research: 3 results,  Peer Reviewed: 13 results,  Open Access: 3 results,  Acknowledgement Compliant: 4 results) Presentation (9 results) (of which Int'l Joint Research: 4 results) Patent(Industrial Property Rights) (2 results) (of which Overseas: 2 results)

  • [Int'l Joint Research] Austin Health(オーストラリア)

    • Related Report
      2016 Annual Research Report
  • [Int'l Joint Research] McGil University(カナダ)

    • Related Report
      2016 Annual Research Report
  • [Journal Article] Monoamine oxidase B inhibitor, selegiline, reduces 18F-THK5351 uptake in the human brain.2017

    • Author(s)
      Ng KP, Pascoal TA, Mathotaarachchi S, Therriault J, Kang MS, Shin M, Guiot MC, Guo Q, Harada R, Comley RA, Massarweh G, Soucy JP, Okamura N, Gauthier S, Rosa-Neto P.
    • Journal Title

      Alzheimers Res Ther.

      Volume: 9:25 Issue: 1 Pages: 25-25

    • DOI

      10.1186/s13195-017-0253-y

    • Related Report
      2016 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Tau imaging with [18F]THK-5351 in progressive supranuclear palsy.2017

    • Author(s)
      Ishiki A, Harada R, Okamura N, Tomita N, Rowe CC, Villemagne VL, Yanai K, Kudo Y, Arai H, Furumoto S, Tashiro M, Furukawa K.
    • Journal Title

      Eur J Neurol.

      Volume: 24 Issue: 1 Pages: 130-136

    • DOI

      10.1111/ene.13164

    • Related Report
      2016 Annual Research Report
    • Peer Reviewed / Int'l Joint Research / Acknowledgement Compliant
  • [Journal Article] 18F-Labeled 2-Arylquinoline Derivatives for Tau Imaging: chemical, radiochemical, biological and clinical features2017

    • Author(s)
      Shozo Furumoto, Tetsuro Tago, Ryuichi Harada, Yukitsuka Kudo, Nobuyuki Okamura
    • Journal Title

      Current Alzheimer Research

      Volume: 14(2) Issue: 2 Pages: 178-185

    • DOI

      10.2174/1567205013666160620121811

    • Related Report
      2016 Annual Research Report
    • Peer Reviewed
  • [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 Annual Research Report
    • Peer Reviewed
  • [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 Annual Research Report
    • Peer Reviewed / Acknowledgement Compliant
  • [Journal Article] microPET Imaging of Tau pathology with [18F]THK-5117 in two Transgenic Mouse Models2016

    • Author(s)
      Matthias Brendel, Anna Jaworska, Federico Probst, Felix Overhoff, Viktoria Korzhova, Simon Lindnerm Janette Carlsen, Peter Bartenstein, Ryuichi Harada, Yukitsuka Kudo, Christian Haass, Fred van Leuven, Nobuyuki Okamura, Jochen Herms, and Axel Rominger
    • Journal Title

      Journal of Nuclear Medicine

      Volume: 印刷中

    • Related Report
      2015 Research-status Report
    • Peer Reviewed / Int'l Joint Research
  • [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
      2015 Research-status Report
    • Peer Reviewed
  • [Journal Article] Characteristics of Tau and Its Ligands in PET Imaging2016

    • Author(s)
      Ryuichi Harada, Nobuyuki Okamura, Shozo Furumoto, Tetsuro Tago, Kazuhiko Yanai, Hiroyuki Arai, Yukitsuka Kudo
    • Journal Title

      Biomolecules

      Volume: 6 Issue: 1 Pages: 1-15

    • DOI

      10.3390/biom6010007

    • Related Report
      2015 Research-status Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [Journal Article] Synthesis and characterization of 18F-interleukin-8 using a cell-free translation system and 18F-fluoro-L-proline, Journal of Nuclear Medicine2016

    • Author(s)
      Ryuichi Harada, Shozo Furumoto, Takeo Yoshikawa, Yoichi Ishikawa, Katsutoshi Shibuya, Nobuyuki Okamura, Kiichi Ishiwata, Ren Iwata, Kazuhiko Yanai
    • Journal Title

      Journal of Nuclear Medicine

      Volume: 57(4) Issue: 4 Pages: 634-639

    • DOI

      10.2967/jnumed.115.162602

    • Related Report
      2015 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
      2015 Research-status Report
    • Peer Reviewed
  • [Journal Article] 18F-THK5351: A Novel PET Radiotracer for Imaging Neurofibrillary Pathology in Alzheimer Disease2016

    • Author(s)
      Harada R, Okamura N, Furumoto S, Furukawa K, Ishiki A, Tomita N, Tago T, Hiraoka K, Watanuki S, Shidahara M, Miyake M, Ishikawa Y, Matsuda R, Inami A, Yoshikawa T, Funaki Y, Iwata R, Tashiro M, Yanai K, Arai H, Kudo Y
    • Journal Title

      J Nucl Med

      Volume: 57 Issue: 2 Pages: 208-214

    • DOI

      10.2967/jnumed.115.164848

    • Related Report
      2015 Research-status Report
    • Peer Reviewed
  • [Journal Article] Longitudinal Assessment of Tau Pathology in Patients with Alzheimer’s Disease Using [18F]THK-5117 Positron Emission Tomography2015

    • Author(s)
      Aiko Ishiki, Nobuyuki Okamura, Katsutoshi Furukawa, Shozo Furumoto, Ryuichi Harada, Naoki Tomita, Kotaro Hiraoka, Shoichi Watanuki, Yoichi Ishikawa, Tetsuro Tago, Yoshihito Funaki, Ren Iwata, Manabu Tashiro, Kazuhiko Yanai, Yukitsuka Kudo, Hiroyuki Arai
    • Journal Title

      PLos One

      Volume: 10(10) Pages: 1-9

    • Related Report
      2015 Research-status Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [Journal Article] Preclinical evaluation of [18F]THK-5015 enantiomers: effects of chirality on its effectiveness as a tau imaging radiotracer.2015

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

      Mol. Imaging Biol.

      Volume: 未定 Issue: 2 Pages: 258-266

    • DOI

      10.1007/s11307-015-0879-8

    • Related Report
      2015 Research-status Report
    • Peer Reviewed
  • [Presentation] Development of a lanthanide complex labeled β-sheet ligand for high-throughput screening using time-resolved fluorescence method2017

    • Author(s)
      原田龍一、岡村信行、古本祥三、吉川雄朗、工藤幸司、谷内一彦
    • Organizer
      第90回日本薬理学会年会
    • Place of Presentation
      長崎新聞文化ホール(長崎県・長崎市)
    • Year and Date
      2017-03-15
    • Related Report
      2016 Annual Research Report
  • [Presentation] Characterizing the “off-target” binding of 18F-THK5351 in Alzheimer’s disease: correlation between ante-mortem and post-mortem findings.2017

    • Author(s)
      Ryuichi Harada, Aiko Ishiki, Shozo Furumoto, Katsutoshi Furukawa, Manabu Tashiro, Arai Hiroyuki, Kazuhiko Yanai, Yukitsuka Kudo, Nobuyuki Okamura
    • Organizer
      11th Human Amyloid Imaging
    • Place of Presentation
      Miami, USA
    • Year and Date
      2017-01-11
    • Related Report
      2016 Annual Research Report
    • Int'l Joint Research
  • [Presentation] 東北大学におけるタウPETプローブの基礎開発研究2016

    • Author(s)
      原田龍一
    • Organizer
      第6回日本認知症予防学会
    • Place of Presentation
      東北大学(宮城県・仙台市)
    • Year and Date
      2016-09-23
    • Related Report
      2016 Annual Research Report
  • [Presentation] Identification of wavelength-dependent compounds for imaging Lewy pathology2016

    • Author(s)
      Ryuichi Harada, Nobuyuki Okamura, Shozo Furumoto, Ren Iwata, Hiroyuki Arai, Kazuhiko Yanai, Yukitsuka Kudo
    • Organizer
      AAIC2016
    • Place of Presentation
      Toronto, Canada
    • Year and Date
      2016-07-22
    • Related Report
      2016 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Metabolite analysis of tau PET tracer [18F]THK-53512016

    • Author(s)
      Ryuichi Harada, Nobuyuki Okamura, Shozo Furumoto, Tetsuro Tago, Katsutoshi Furukawa, Aiko Ishiki, Ren Iwata, Manabu Tashiro, Hiroyuki Arai, Kazuhiko Yanai, Yukitsuka Kudo
    • Organizer
      Human Amyloid Imaging Conference 2016
    • Place of Presentation
      Miami, USA
    • Year and Date
      2016-01-14
    • Related Report
      2015 Research-status Report
    • Int'l Joint Research
  • [Presentation] タウイメージングトレーサーの[18F]THK-5351の代謝解析2015

    • Author(s)
      原田龍一、岡村信行、古本祥三、多胡哲郎、岩田錬、谷内一彦、工藤幸司
    • Organizer
      第55回日本核医学会学術総会
    • Place of Presentation
      ハイアットリージェンシー東京(東京都・新宿区)
    • Year and Date
      2015-11-05
    • Related Report
      2015 Research-status Report
  • [Presentation] タウPETプローブ[18F]THK-5351の結合特性の解析2015

    • Author(s)
      原田龍一、岡村信行、古本祥三、古川勝敏、石木愛子、岩田錬、谷内一彦、荒井啓行、工藤幸司
    • Organizer
      第34回日本認知症学会
    • Place of Presentation
      リンクステーション青森(青森県・青森市)
    • Year and Date
      2015-10-04
    • Related Report
      2015 Research-status Report
  • [Presentation] Validation of the binding specificity of tau PET tracer [18F]THK-5351 on postmortem human brain samples2015

    • Author(s)
      Ryuichi Harada, Nobuyuki Okamura, Shozo Furumoto, Aiko Ishiki, Katsutoshi Furukawa, Tomita Naoki, Tetsuro Tago, Ren Iwata, Kazuhiko Yanai, Hiroyuki Arai, Yukitsuka Kudo
    • Organizer
      AAIC2015
    • Place of Presentation
      Washington D.C., USA
    • Year and Date
      2015-07-22
    • Related Report
      2015 Research-status Report
    • Int'l Joint Research
  • [Presentation] Characterization of [18F]THK-5351 for imaging of tau pathology in Alzheimer's disease2015

    • Author(s)
      Ryuichi Harada, Nobuyuki Okamura, Shozo Furumoto, Testuro Tago, Ren Iwata, Kazuhiko Yanai, Hiroyuki Arai, Yukitsuka Kudo
    • Organizer
      第10回日本分子イメージング学会
    • Place of Presentation
      タワーホール船堀(東京都・江戸川区)
    • Year and Date
      2015-05-18
    • Related Report
      2015 Research-status Report
  • [Patent(Industrial Property Rights)] MONOAMINE OXIDASE B BINDERS2016

    • Inventor(s)
      古本祥三、工藤幸司、岡村信行、原田龍一
    • Industrial Property Rights Holder
      古本祥三、工藤幸司、岡村信行、原田龍一
    • Industrial Property Rights Type
      特許
    • Filing Date
      2016-12-18
    • Related Report
      2016 Annual Research Report
    • Overseas
  • [Patent(Industrial Property Rights)] MONOAMINE OXIDASE B BINDERS2015

    • Inventor(s)
      古本祥三、岡村信行、工藤幸司、原田龍一
    • Industrial Property Rights Holder
      古本祥三、岡村信行、工藤幸司、原田龍一
    • Industrial Property Rights Type
      特許
    • Filing Date
      2015-12-18
    • Related Report
      2015 Research-status Report
    • Overseas

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Published: 2015-04-16   Modified: 2018-03-22  

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