Comparative study of tau imaging tracers

• Project/Area Number: 15K19767
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Radiation science
• Research Institution: Tohoku 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: ¥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.

Research Products

• [Int'l Joint Research] Austin Health(オーストラリア)
• [Int'l Joint Research] McGil University(カナダ)
• [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
  • 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
  • Peer Reviewed / Int'l Joint Research / Acknowledgement Compliant
• [Journal Article] 18F-Labeled 2-Arylquinoline Derivatives for Tau Imaging: chemical, radiochemical, biological and clinical features (2017)
  • 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
  • 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
  • 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
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] microPET Imaging of Tau pathology with [18F]THK-5117 in two Transgenic Mouse Models (2016)
  • 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
  • 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
  • Peer Reviewed
• [Journal Article] Characteristics of Tau and Its Ligands in PET Imaging (2016)
  • 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
  • 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 Medicine (2016)
  • 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
  • Peer Reviewed
• [Journal Article] Structure-Activity Relationship of 2-Arylquinolines as PET Imaging Tracers for Tau Pathology in Alzheimer’s Disease (2016)
  • 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
  • Peer Reviewed
• [Journal Article] 18F-THK5351: A Novel PET Radiotracer for Imaging Neurofibrillary Pathology in Alzheimer Disease (2016)
  • 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
  • Peer Reviewed
• [Journal Article] Longitudinal Assessment of Tau Pathology in Patients with Alzheimer’s Disease Using [18F]THK-5117 Positron Emission Tomography (2015)
  • 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
  • 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
  • Peer Reviewed
• [Presentation] Development of a lanthanide complex labeled β-sheet ligand for high-throughput screening using time-resolved fluorescence method (2017)
  • 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
• [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
  • 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
• [Presentation] Identification of wavelength-dependent compounds for imaging Lewy pathology (2016)
  • 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
  • Int'l Joint Research
• [Presentation] Metabolite analysis of tau PET tracer [18F]THK-5351 (2016)
  • 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
  • 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
• [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
• [Presentation] Validation of the binding specificity of tau PET tracer [18F]THK-5351 on postmortem human brain samples (2015)
  • 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
  • Int'l Joint Research
• [Presentation] Characterization of [18F]THK-5351 for imaging of tau pathology in Alzheimer's disease (2015)
  • 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
• [Patent(Industrial Property Rights)] MONOAMINE OXIDASE B BINDERS (2016)
  • 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
  • Overseas
• [Patent(Industrial Property Rights)] MONOAMINE OXIDASE B BINDERS (2015)
  • 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
  • Overseas