タウ蛋白検出ＰＥＴプローブの臨床応用

2013 Fiscal Year Annual Research Report

• Project/Area Number: 23390297
• Research Institution: Tohoku University
• Principal Investigator: 岡村 信行 東北大学, 医学(系)研究科(研究院), 准教授 (40361076)
• Project Period (FY): 2011-04-01 – 2014-03-31
• Keywords: 痴呆 / 神経科学 / 放射線 / 脳神経疾患 / 老化

Research Abstract

本年度は研究代表者らが独自に開発したタウイメージング用PETプローブ[18F]THK-5117のFirst-in-man studyを東北大学サイクロトロンRIセンターで実施した。健常高齢者6名、アルツハイマー病患者8名の計14名を対象に[18F]THK-5117を用いたPETスキャンを実施した。185MBqの[18F]THK-5117投与後、90分間のPET撮像を行い、トレーサー集積の指標として投与60－80分後のSUV対小脳比を算出した。また同一被検者で[11C]PiB-PET検査を併せて実施した。その結果、アルツハイマー病患者における[18F]THK-5117の集積は側頭葉・海馬領域を中心に認められ、タウ病理像の分布と一致し、前頭葉や楔前部において強い集積を示す[11C]PiBとは異なる集積分布を示した。アルツハイマー病患者における[18F]THK-5117集積量は認知症の重症化に伴って上昇する傾向を認め、海馬容積と負の相関を示した。以上の結果から、[18F]THK-5117は脳内タウ病理像を選択的に検出し、従来のアミロイドPETとは異なる情報を提供するPETプローブであることが確認された。またこれと並行して、アルツハイマー病やその他のタウオパチー疾患の脳組織標本を用いて、プローブの詳細な結合性について検討を加えた。その結果、THK-5117はアルツハイマー病の神経原線維変化、ニューロピルスレッドに加えて、皮質基底核変性症の嗜銀性スレッドにも結合し、アルツハイマー病以外のタウオパチー病変にも結合する能力をもつことが示唆された。以上、当初の目標通り、臨床研究において研究代表者らが開発したPETプローブ[18F]THK-5117の臨床的有用性を証明することができた。

Current Status of Research Progress

Reason

25年度が最終年度であるため、記入しない。

Strategy for Future Research Activity

25年度が最終年度であるため、記入しない。

Research Products

• [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: 137 Pages: 印刷中
  • Peer Reviewed
• [Journal Article] Assessing THK523 selectivity for tau deposits in Alzheimer's disease and non Alzheimer's disease tauopathies. (2014)
  • Author(s): Fodero-Tavoletti MT, Furumoto S, Taylor L, McLean CA, Mulligan RS, Birchall I, Harada R, Masters CL, Yanai K, Kudo Y, Rowe CC, Okamura N, Villemagne VL.
  • Journal Title: Alzheimer's Research & Therapy Volume: 6 Pages: 印刷中
  • Peer Reviewed
• [Journal Article] In vivo evaluation of a novel tau imaging tracer for Alzheimer's disease. (2014)
  • Author(s): Villemagne VL, Furumoto S, Fodero-Tavoletti MT, Mulligan RS, Hodges J, Harada R, Yates P, Piguet O, Pejoska S, Dore V, Yanai K, Masters CL, Kudo Y, Rowe CC, Okamura N.
  • Journal Title: European Journal of Nuclear Medicine and Molecular Imaging Volume: 41 Pages: 816-826
  • DOI: 10.1007/s00259-013-2681-7.
  • Peer Reviewed
• [Journal Article] Synthesis and preliminary evaluation of 2-arylhydroxyquinoline derivatives for tau imaging. (2014)
  • Author(s): Tago T, Furumoto S, Okamura N, Harada R, Ishikawa Y, Arai H, Yanai K, Iwata R, Kudo Y.
  • Journal Title: Journal of Labelled Compounds and Radiopharmaceuticals Volume: 57 Pages: 18-24
  • DOI: 10.1002/jlcr.3133.
  • Peer Reviewed
• [Journal Article] Use of a benzimidazole derivative BF-188 in fluorescence multispectral imaging for selective visualization of tau protein fibrils in the Alzheimer's disease brain. (2014)
  • Author(s): Harada R, Okamura N, Furumoto S, Yoshikawa T, Arai H, Yanai K, Kudo Y.
  • Journal Title: Molecular Imaging and Biology Volume: 16 Pages: 19-27
  • DOI: 10.1007/s11307-013-0667-2.
  • Peer Reviewed
• [Journal Article] Imaging of amyloid deposition in human brain using positron emission tomography and [18F]FACT: comparison with [11C]PIB. (2014)
  • Author(s): Ito H, Shinotoh H, Shimada H, Miyoshi M, Yanai K, Okamura N, Takano H, Takahashi H, Arakawa R, Kodaka F, Ono M, Eguchi Y, Higuchi M, Fukumura T, Suhara T.
  • Journal Title: European Journal of Nuclear Medicine and Molecular Imaging Volume: 41 Pages: 印刷中
  • Peer Reviewed
• [Journal Article] Analysis of early phase [11C]BF-227 PET, and its application for anatomical standardization of late-phase images for 3D-SSP analysis. (2014)
  • Author(s): Kaneta T, Okamura N, Arai A, Takanami K, Furukawa K, Tashiro M, Furumoto S, Iwata R, Takahashi S, Arai H, Yanai K, Kudo Y.
  • Journal Title: Japanese Journal of Radiology Volume: 32 Pages: 138-144
  • DOI: 10.1007/s11604-013-0276-7.
  • Peer Reviewed
• [Journal Article] Imaging of tau pathology in a tauopathy mouse model and in Alzheimer patients compared to normal controls. (2013)
  • Author(s): Maruyama M, Shimada H, Suhara T, Shinotoh H, Ji B, Maeda J, Zhang MR, Trojanowski JQ, Lee VM, Ono M, Masamoto K, Takano H, Sahara N, Iwata N, Okamura N, Furumoto S, Kudo Y, Chang Q, Saido TC, Takashima A, Lewis J, Jang MK, Aoki I, Ito H, Higuchi M.
  • Journal Title: Neuron Volume: 79 Pages: 1094-1108
  • DOI: 10.1016/j.neuron.2013.07.037.
  • Peer Reviewed
• [Journal Article] Novel 18F-labeled arylquinoline derivatives for noninvasive imaging of tau pathology in Alzheimer disease. (2013)
  • Author(s): Okamura N, Furumoto S, Harada R, Tago T, Yoshikawa T, Fodero-Tavoletti M, Mulligan RS, Villemagne VL, Akatsu H, Yamamoto T, Arai H, Iwata R, Yanai K, Kudo Y.
  • Journal Title: Journal of Nuclear Medicine Volume: 54 Pages: 1420-1427
  • DOI: 10.2967/jnumed.112.117341.
  • Peer Reviewed
• [Journal Article] A 18F-labeled BF-227 derivative as a potential radioligand for imaging dense amyloid plaques by positron emission tomography. (2013)
  • Author(s): Furumoto S, Okamura N, Furukawa K, Tashiro M, Ishikawa Y, Sugi K, Tomita N, Waragai M, Harada R, Tago T, Iwata R, Yanai K, Arai H, Kudo Y.
  • Journal Title: Molecular Imaging and Biology Volume: 15 Pages: 497-506
  • DOI: 10.1007/s11307-012-0608-5.
  • Peer Reviewed
• [Presentation] PET tau imaging in Alzheimer’s disease using 18F-THK5105 and 18F-THK5117. (2014)
  • Author(s): Okamura N, Harada R, Furumoto S, Yanai K, Arai H, Kudo Y.
  • Organizer: The 87th Annual Meeting of The Japanese Pharmacological Society
  • Place of Presentation: 仙台
  • Year and Date: 20140321-20140321
• [Presentation] Tau PET imaging in Alzheimer’s disease using novel 2-phenylquinoline derivatives. (2014)
  • Author(s): Okamura N.
  • Organizer: The Fifteenth Conference of Peace through Mind Brain Science
  • Place of Presentation: 浜松
  • Year and Date: 20140219-20140219
  • Invited
• [Presentation] PET imaging of tau deposits in Alzheimer's disease patients using 18F-THK5105 and 18F-THK5117. (2014)
  • Author(s): Okamura N, Furumoto S, Harada R, Furukawa K, Ishiki A, Fodero-Tavoletti MT, Mulligan RS, Iwata R, Tashiro M, Yanai K, Masters CL, Arai H, Rowe CC, Villemagne VL, Kudo Y.
  • Organizer: Human Amyloid Imaging 2014
  • Place of Presentation: Miami, USA
  • Year and Date: 20140116-20140116
• [Presentation] PET imaging of tau pathology in patients with Alzheimer's disease using 18F-THK5117. (2013)
  • Author(s): Okamura N, Furumoto S, Harada R, Furukawa K, Ishiki A, Tomita N, Iwata R, Tashiro M, Yanai K, Arai H, Kudo Y.
  • Organizer: Clinical Trials on Alzheimer's Disease (CtaD) 2013
  • Place of Presentation: San Diego, USA
  • Year and Date: 20131114-20131114
• [Presentation] アルツハイマー病患者における[18F]THK-5105, [18F]THK-5117の臨床評価． (2013)
  • Author(s): 岡村信行、古本祥三、原田龍一、多胡哲郎、古川勝敏、石木愛子、冨田尚希、平岡宏太良、四月朔日聖一、松田林、石川洋一、田代学、岩田錬、谷内一彦、荒井啓行、工藤幸司、Rachel S Mulligan、Christopher C Rowe、Victor L Villemagne．
  • Organizer: 第53回日本核医学会学術総会
  • Place of Presentation: 福岡
  • Year and Date: 20131108-20131108
• [Presentation] [18F]THK-5105 PETを用いたアルツハイマー病タウ病理像の生体画像化 (2013)
  • Author(s): 岡村信行、古本祥三、原田龍一、古川勝敏、石木愛子、冨田尚希、荒井啓行、谷内一彦、工藤幸司、Rachel S Mulligan、Christopher C Rowe、Victor L Villemagne．
  • Organizer: 第32回日本認知症学会学術集会
  • Place of Presentation: 松本
  • Year and Date: 20131108-20131108
• [Presentation] Imaging tau pathology in Alzheimer's disease using 18F-THK5105 and 18F-THK5117 PET. (2013)
  • Author(s): Okamura N.
  • Organizer: ADNI PPSB meeting
  • Place of Presentation: Washington DC, USA
  • Year and Date: 20131026-20131026
  • Invited
• [Presentation] Imaging prion and other misfolded protein deposits using PET. (2013)
  • Author(s): Okamura N.
  • Organizer: Asia Pacific Prion Symposium (APPS)
  • Place of Presentation: 長崎
  • Year and Date: 20130721-20130721
  • Invited
• [Presentation] In vivo pattern of tau and Aβ deposition in the brain might distinguish healthy controls from preclinical Alzheimer's disease. (2013)
  • Author(s): Villemagne VL Furumoto S, Fodero-Tavoletti MT, Mulligan RS, Harada R, Yates P, Pejoska S, Kudo Y, Masters CL, Yanai K, Rowe CC, Okamura N.
  • Organizer: Alzheimer’s Association International Conference(AAIC) 2013
  • Place of Presentation: Boston, USA
  • Year and Date: 20130716-20130716
• [Presentation] In vivo detection of tau protein deposits in Alzheimer's disease using 18F-labeled 2-phenylquinoline derivatives. (2013)
  • Author(s): Okamura N, Furumoto S, Harada R, Fodero-Tavoletti MT, Mulligan RS, Masters CL, Yanai K, Kudo Y, Rowe CC, Villemagne VL.
  • Organizer: Alzheimer’s Association International Conference(AAIC) 2013
  • Place of Presentation: Boston, USA
  • Year and Date: 20130713-20130717
• [Presentation] PET tau imaging in Alzheimer's disease using novel 18F-labeled 2-phenylquinoline derivatives. (2013)
  • Author(s): Okamura N, Furumoto S, Harada R, Fodero-Tavoletti MT, Mulligan RS, Masters CL, Yanai K, Kudo Y, Rowe CC, Villemagne VL.
  • Organizer: SNMMI Annual Meeting
  • Place of Presentation: Vancouver, Canada
  • Year and Date: 20130611-20130611
• [Presentation] [18F]THK-5105を用いたアルツハイマー病脳内タウ蛋白のPETイメージング (2013)
  • Author(s): 岡村信行、古本祥三、原田龍一、多胡哲郎、岩田錬、谷内一彦、工藤幸司、Michelle T Fodero-Tavoletti、Christopher C Rowe、Victor L. Villemagne.
  • Organizer: 第8回日本分子イメージング学会総会・学術総会
  • Place of Presentation: 横浜
  • Year and Date: 20130530-20130530