Precise evaluation and optimization of the THK probe for tau imaging

• Project/Area Number: 25293259
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Partial Multi-year Fund
• Section: 一般
• Research Field: Radiation science
• Research Institution: Tohoku University
• Principal Investigator: FURUMOTO SHOZO 東北大学, サイクロトロン・ラジオアイソトープセンター, 教授 (00375198)
• Co-Investigator(Renkei-kenkyūsha): OKAMURA Nobuyuki 東北大学, 大学院医学系研究科, 准教授 (40361076) ; SHIDAHARA Miho 東北大学, 大学院医学系研究科, 講師 (20443070)
• Project Period (FY): 2013-04-01 – 2016-03-31
• Project Status: Completed (Fiscal Year 2015)
• Budget Amount: ¥18,460,000 (Direct Cost: ¥14,200,000、Indirect Cost: ¥4,260,000); Fiscal Year 2015: ¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000); Fiscal Year 2014: ¥6,110,000 (Direct Cost: ¥4,700,000、Indirect Cost: ¥1,410,000); Fiscal Year 2013: ¥8,060,000 (Direct Cost: ¥6,200,000、Indirect Cost: ¥1,860,000)
• Keywords: タウ / PET / イメージング / 18F

Outline of Final Research Achievements

Alzheimer's disease (AD) is the most common form of dementia in the elderly. Abnormal deposition of phosphorylated tau is one of the key pathological changes in the AD brain. The purpose of this study is to optimize the chemical structure of THK tau PET probes that have been developed by us for imaging tau pathology in the AD brain with PET. One modification of the probe structure was replacement of the benzene ring to pyridinyl one. Another change was conformational optimization of the fluoropropanol side chain. S-enantiomer of the pyridinyl derivative showed better brain pharmacokinetics in normal mice. The optimized derivative indicated lower non-specific binding to white matter of the AD brain tissue samples. Clinical PET study using the optimized probe demonstrated that higher radioactivity uptakes were observed in the parahippocampal gyrus and inferior temporal gyrus. These results suggest the potential utility of the optimized THK tau probe.

Research Products

• [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] 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
• [Journal Article] タウプローブ開発の最先端 (2014)
  • Author(s): 古本 祥三, 岡村 信行, 原田 龍一, 多胡 哲朗, 工藤 幸司
  • Journal Title: JSMI Report Volume: 8 Pages: 3-7
  • Peer Reviewed
• [Journal Article] 18F標識PETプローブの現状と展望 (2014)
  • Author(s): 古本祥三
  • Journal Title: INNERVISION Volume: 29 Pages: 11-14
• [Journal Article] Non-invasive assessment of Alzheimer's disease neurofibrillary pathology using 18F-THK5105 PET. (2014)
  • Author(s): Nobuyuki Okamura, Shozo Furumoto, Michelle T. Fodero-Tavoletti, Rachel S. Mulligan, Ryuichi Harada, Paul Yates, Svetlana Pejoska, Yukitsuka Kudo, Colin L. Masters, Kazuhiko Yanai, Christopher C. Rowe, Victor L. Villemagne
  • Journal Title: Brain Volume: 137 Pages: 1762-1771
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] In vivo evaluation of a novel tau imaging tracer for Alzheimer's disease (2014)
  • Author(s): Villemagne L. Victor, Shozo Furumoto, Michelle T. Fodero-Tavoletti, Rachel S. Mulligan, John Hodges, Ryuichi Harada, Paul Yates, Oliver Piguet, Svetlana Pejoska, Vincent Doré, Kazuhiko Yanai, Colin L. Masters, Yukitsuka Kudo, Christopher C. Rowe, Nobuyuki Okamura.
  • Journal Title: European Journal of Nuclear Medicine and Molecular Imaging Volume: 41 Issue: 5 Pages: 816-826
  • DOI: 10.1007/s00259-013-2681-7
  • Peer Reviewed / Open Access
• [Journal Article] Non-invasive assessment of Alzheimer's disease neurofibrillary pathology using 18F-THK5105 PET. (2014)
  • Author(s): Okamura N, Furumoto S, Fodero-Tavoletti MT, Mulligan RS, Harada R, Yates P, Pejoska S, Kudo Y, Masters CL, Yanai K, Rowe CC, Villemagne VL.
  • Journal Title: Brain Volume: 印刷中
  • Peer Reviewed
• [Presentation] PETによるアルツハイマー病タウイメージングのための2-アリールキノリン誘導体開発 (2015)
  • Author(s): 多胡哲郎，古本祥三，岡村信行，原田龍一，安立創，石川洋一，谷内一彦，工藤幸司，岩田錬
  • Organizer: 第 55 回日本核医学会学術総会
  • Place of Presentation: 東京
  • Year and Date: 2015-11-05
• [Presentation] タウイメージングトレーサー[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: 東京
  • Year and Date: 2015-11-05
• [Presentation] PETプローブの創製研究 ～分子設計から橋渡し研究まで～ (2015)
  • Author(s): 古本祥三
  • Organizer: 平成27年度日本薬学会東北支部総会・学術講演会
  • Place of Presentation: 仙台
  • Year and Date: 2015-06-13
  • Invited
• [Presentation] Preclinical characterization of [18F]THK-5117 enantiomers as a PET tau probe for tau pathology in Alzheimer’s disease (2015)
  • Author(s): T. Tago, S. Furumoto, N. Okamura, R. Harada, H. Adachi, Y. Ishikawa, K. Yanai, R. Iwata, Y. Kudo.
  • Organizer: 21st International Symposium on Radiopharmaceutical Sciences
  • Place of Presentation: Columbia, Missouri
  • Year and Date: 2015-05-26
  • Int'l Joint Research
• [Presentation] 2-アリールキノリン PET タウイメージング剤の構造活性相関研究 (2015)
  • Author(s): 多胡哲郎，古本祥三，岡村信行，原田龍一，石川洋一，谷内一彦，岩田錬，工藤幸司
  • Organizer: 日本分子イメージング学会第 10 回総会・学術集会
  • Place of Presentation: 東京
  • Year and Date: 2015-05-20
• [Presentation] Chirality of [18F]THK-5105 Affects its Preclinical Characteristics as a PET Tau Imaging Probe (2015)
  • Author(s): Tago T, Furumoto S, Okamura N, Harada R, Adachi H, Ishikawa Y, Yanai K, Iwata R, Kudo Y
  • Organizer: 9th Human Amyloid Imaging 2015
  • Place of Presentation: 米国マイアミ
  • Year and Date: 2015-01-14 – 2015-01-16
• [Presentation] PET用タウイメージング剤[18F]THK-5105のエナンチオマー体の詳細評価 (2014)
  • Author(s): 多胡 哲郎, 古本 祥三, 岡村 信行, 原田 龍一, 安立 創, 石川 洋一, 谷内 一彦, 工藤 幸司, 岩田 錬
  • Organizer: 第54回日本核医学会学術総会
  • Place of Presentation: 大阪
  • Year and Date: 2014-11-06 – 2014-11-08
• [Presentation] Accumulation of the novel tau imaging tracer, 18F-5117 is associated with brain atrophy in Alzheimer's disease. (2014)
  • Author(s): Ishiki A, Furumoto S, Harada R, Furukawa K, Okamura N, Tashiro M, Yanai K, Kudo Y, Arai H
  • Organizer: Alzheimer's Association International Conference 2014
  • Place of Presentation: コペンハーゲン
  • Year and Date: 2014-07-12 – 2014-07-17
• [Presentation] In vivo selective imaging of tau pathology in Alzheimer's disease with 18F-THK5117 (2014)
  • Author(s): Okamura N, Furumoto S, Harada R, Furukawa K, Ishiki A, Iwata R, Tashiro M, Yanai K, Arai H, Kudo Y.
  • Organizer: Society of Nuclear Medicine and Molecular Imaging 2014
  • Place of Presentation: 米国セントルイス
  • Year and Date: 2014-06-07 – 2014-06-11
• [Presentation] Tau Probe Development: From A Molecular Design To A Clinical Research. (2014)
  • Author(s): Furumoto S., Okamura N., Kudo Y.
  • Organizer: 第9回日本分子イメージング学会総会・学術集会
  • Place of Presentation: 大阪千里
  • Year and Date: 2014-05-22 – 2014-05-23
• [Presentation] PET用タウイメージング剤[18F]THK-5105エナンチオマー体の評価 (2014)
  • Author(s): 多胡 哲郎, 古本 祥三, 岡村 信行, 原田 龍一, 安立 創, 石川 洋一, 谷内 一彦, 工藤 幸司, 岩田 錬
  • Organizer: 第9回日本分子イメージング学会総会・学術集会
  • Place of Presentation: 大阪千里
  • Year and Date: 2014-05-22 – 2014-05-23
• [Presentation] PET用タウイメージング剤[18F]THK5105のエナンチオマー体の合成と評価 (2013)
  • Author(s): 多胡哲朗、古本祥三、岡村信行、原田龍一、石川洋一、谷内一彦、工藤幸司、岩田錬
  • Organizer: 第53回日本核医学会学術総会
  • Place of Presentation: 福岡
• [Presentation] アルツハイマー病患者における[18F]THK5105の臨床評価 (2013)
  • Author(s): 岡村信行、古本祥三、原田龍一、多胡哲朗、谷内一彦、レイチェルマリガン、クリストファーロウ、ビクタービルマーニ
  • Organizer: 第53回日本核医学会学術総会
  • Place of Presentation: 福岡