Development of amyloid and tau imaging probes for early diagnosis of dementia

• Project/Area Number: 20591432
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Radiation science
• Research Institution: Tohoku University
• Principal Investigator: OKAMURA Nobuyuki Tohoku University, 大学院・医学系・研究科, 准教授 (40361076)
• Project Period (FY): 2008 – 2010
• Project Status: Completed (Fiscal Year 2010)
• Budget Amount: ¥4,550,000 (Direct Cost: ¥3,500,000、Indirect Cost: ¥1,050,000); Fiscal Year 2010: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000); Fiscal Year 2009: ¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000); Fiscal Year 2008: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
• Keywords: 認知症 / 神経科学 / 放射線 / 脳神経疾患 / 老化 / PET / アルツハイマー病 / アミロイドβ蛋白

Research Abstract

Noninvasive visualization of amyloid-ss (Ass) and tau deposits in the living brain will contribute to a better understanding of the pathophysiology of Alzheimer's disease (AD). Although in vivo Ass imaging probes for positron emission tomography (PET) are currently available, in vivo tau imaging agent is still unavailable for clinical study. As candidate probes for PET tau imaging, we developed novel compounds named [^<18>F]THK-523 and [^<11>C]THK-951. These two compounds showed high binding affinity and specificity to tau protein and high brain-blood barrier permeability.

Research Products

• [Journal Article] [^<18>F]-THK523, a novel in vivo tau imaging ligand for Alzheimer's disease. (2011)
  • Author(s): Fodero-Tavoletti MT, Okamura N, Furumoto S, Mulligan RS, Connor A, McLean CA, Cao D, Rigopoulos A, O'Keefe G, Gong S, Adlard PA, Barnham KJ, Rowe CC, Masters CL, Kudo Y, Cappai R, Yanai K, Villemagne VL.
  • Journal Title: Brain 134 Pages: 1089-1100
  • Peer Reviewed
• [Journal Article] [^<18>F]-THK523, a novel in vivo tau imaging ligand for Alzheimer's disease. (2011)
  • Author(s): Fodero-Tavoletti MT, et al.
  • Journal Title: Brain Volume: 134 Pages: 1089-1100
  • Peer Reviewed
• [Journal Article] In vivo detection of amyloid plaques in the mouse brain using the near-infrared fluorescence probe THK-265. (2011)
  • Author(s): Okamura N, et al.
  • Journal Title: J Alzheimers Dis Volume: 23 Pages: 37-48
  • Peer Reviewed
• [Journal Article] In vivo detection of prion amyloid plaques using [^<11>C]BF-227 PET. (2010)
  • Author(s): Okamura N, Shiga Y, Furumoto S, Tashiro M, Tsuboi Y, Furukawa K, Yanai K, Iwata R, Arai H, Kudo Y, Itoyama Y, Doh-ura K.
  • Journal Title: Eur J Nucl Med Mol Imaging. 37 Pages: 934-941
  • Peer Reviewed
• [Journal Article] In vivo measurement of vesicular monoamine transporter type 2 density in Parkinson's disease with ^<18>F-AV-133. (2010)
  • Author(s): Okamura N, Villemagne VL, Drago J, Pejoska S, Dhamija RK, Mulligan RS, Ellis JR, Ackermann U, O'Keefe G, Jones G, Hughes A, Kung HF, Pontecorvo MJ, Skovronsky D, Rowe CC.
  • Journal Title: J Nucl Med. 51 Pages: 223-228
  • Peer Reviewed
• [Journal Article] Voxel-based analysis of amyloid PET probe [^<11>C]BF-227 uptake in mild cognitive impairment and Alzheimer's disease. (2010)
  • Author(s): Shao H, Okamura N, Sugi K, Furumoto S, Furukawa K, Tashiro M, Iwata R, Matsuda H, Kudo Y, Arai H, Fukuda H, Yanai K.
  • Journal Title: Dement Geriatr Cogn Disord. 30 Pages: 101-111
  • Peer Reviewed
• [Journal Article] In vivo visualization of α-synuclein deposition by [^<11>C]-BF-227 PET in multiple system atrophy. (2010)
  • Author(s): Kikuchi A, Takeda A, Okamura N, Tashiro M, Hasegawa T, Furumoto S, Kobayashi M, Sugeno N, Baba T, Miki Y, Mori F, Wakabayashi K, Funaki Y, Fukuda H, Arai H, Kudo Y, Yanai K, Itoyama Y.
  • Journal Title: Brain 133 Pages: 1772-1778
  • Peer Reviewed
• [Journal Article] Amyloid PET in mild cognitive impairment and Alzheimer's disease with BF-227: Comparison to FDG-PET. (2010)
  • Author(s): Furukawa K, Okamura N, Tashiro M, Waragai M, Furumoto S, Iwata R, Yanai K, Kudo Y, Arai H.
  • Journal Title: J Neurol. 257 Pages: 721-727
  • Peer Reviewed
• [Journal Article] Geriatric medicine, Japanese Alzheimer's disease neuroimaging initiative and biomarker development (2010)
  • Author(s): Arai H, Okamura N, Furukawa K, Kudo Y.
  • Journal Title: Tohoku J Exp Med. 221 Pages: 87-95
  • NAID: 10027084541
  • Peer Reviewed
• [Journal Article] Next-day residual sedative effect after nighttime administration of an over-the-counter antihistamine sleep aid, diphenhydramine, measured by positron emission tomography. (2010)
  • Author(s): Zhang D, Tashiro M, Shibuya K, Okamura N, Funaki Y, Yoshikawa T, Kato M, Yanai K.
  • Journal Title: J Clin Psychopharmacol. 30 Pages: 694-701
  • Peer Reviewed
• [Journal Article] Roles of hypothalamic subgroup histamine and orexin neurons on behavioral responses to sleep deprivation induced by the treadmill method in adolescent rats. (2010)
  • Author(s): Xu A, Sakurai E, Kuramasu A, Zhang J, Li J, Okamura N, Zhang D, Yoshikawa T, Watanabe T, Yanai K.
  • Journal Title: J Pharmacol Sci. 114 Pages: 444-453
  • NAID: 10029891159
  • Peer Reviewed
• [Journal Article] Florbetapir (^<18>F), a PET imaging agent that binds to amyloid plaques for detection of Alzheimer's disease. (2010)
  • Author(s): Okamura N, Yanai K.
  • Journal Title: IDrugs 13 Pages: 890-899
  • Peer Reviewed
• [Journal Article] In vivo visualization of α-synuclein deposition by [11C]-BF-227 PET in multiple system atrophy. (2010)
  • Author(s): Kikuchi A, et al.
  • Journal Title: Brain Volume: 133 Pages: 1772-1778
  • Peer Reviewed
• [Journal Article] In vivo detection of prion amyloid plaques using[11C]BF-227 PET. (2010)
  • Author(s): Okamura N, et al.
  • Journal Title: European Journal of Nuclear Medicine and Molecular Imaging 37 Pages: 934-941
  • Peer Reviewed
• [Journal Article] In vivo measurement of vesicular monoamine transporter type 2 density in parkinson disease with(18)F-AV-133. (2010)
  • Author(s): Okamura N, et al.
  • Journal Title: Journal of Nuclear Medicine 51 Pages: 223-228
  • Peer Reviewed
• [Journal Article] Advances in molecular imaging for the diagnosis of dementia. (2009)
  • Author(s): Okamura N, Fodero-Tavoletti MT, Kudo Y, Rowe CC, Furumoto S, Arai H, Masters CL, Yanai K, Villemagne VL.
  • Journal Title: Expert Opin.Med.Diagn. 3 Pages: 705-716
  • Peer Reviewed
• [Journal Article] Comparison study of amyloid PET and voxel-based morphometry analysis in mild cognitive impairment and Alzheimer's disease. (2009)
  • Author(s): Waragai M, Okamura N, Furukawa K, Tashiro M, Furumoto S, Funaki Y, Kato M, Iwata R, Yanai K, Kudo Y, Arai H.
  • Journal Title: J Neurol Sci. 285 Pages: 100-108
  • Peer Reviewed
• [Journal Article] Methamphetamine- and 3,4-methylenedioxymethamphetamine-induced behavioral changes in histamine H3-receptor knockout mice. (2009)
  • Author(s): Okuda T, Zhang D, Shao H, Okamura N, Takino N, Iwamura T, Sakurai E, Yoshikawa T, Yanai K.
  • Journal Title: J Pharmacol Sci. 111 Pages: 167-174
  • Peer Reviewed
• [Journal Article] In vitro characterisation of BF227 binding to alpha-synuclein/Lewy bodies. (2009)
  • Author(s): Fodero-Tavoletti MT, Mulligan RS, Okamura N, Furumoto S, Rowe CC, Kudo Y, Masters CL, Cappai R, Yanai K, Villemagne VL.
  • Journal Title: Eur J Pharmacol. 617 Pages: 54-58
  • Peer Reviewed
• [Journal Article] Quantitative analysis of donepezil binding to acetylcholinesterase using positron emission tomography and [5-^<11>C-methoxy]donepezil. (2009)
  • Author(s): Hiraoka K, Okamura N, Funaki Y, Watanuki S, Tashiro M, Kato M, Hayashi A, Hosokai Y, Yamasaki H, Fujii T, Mori E, Yanai K, Watabe H.
  • Journal Title: Neuroimage. 46 Pages: 616-623
  • Peer Reviewed
• [Journal Article] Comparison study of amyloid PET and voxel-based morphometry analysis in mild cognitive impairment and Alzheimer's disease. (2009)
  • Author(s): Waragai, et al.
  • Journal Title: Journal of the Neurological Sciences 285 Pages: 100-108
  • Peer Reviewed
• [Journal Article] In vivo visualization of donepezil binding in the brain of patients with Alzheimer's disease. (2008)
  • Author(s): Okamura N, Funaki Y, Tashiro M, Kato M, Ishikawa Y, Maruyama M, Ishikawa H, Meguro K, Iwata R, Yanai K.
  • Journal Title: Br J Clin Pharmacol. 65 Pages: 472-479
  • Peer Reviewed
• [Journal Article] Imaging amyloid pathology in the living brain. (2008)
  • Author(s): Okamura N, Furumoto S, Arai H, Iwata R, Yanai K, Kudo Y.
  • Journal Title: Curr Med Imaging Rev. 4 Pages: 56-62
• [Journal Article] Discrete cortical regions associated with the musical beauty of major and minor chords. (2008)
  • Author(s): Suzuki M, Okamura N, Kawachi Y, Tashiro M, Arao H, Hoshishiba T, Gyoba J, Yanai K.
  • Journal Title: Cogn Affect Behav Neurosci. 8 Pages: 126-131
  • Peer Reviewed
• [Journal Article] Blocking histamine H_1 improves learning and mnemonic dysfunction in mice with social isolation plus repeated methamphetamine injection. (2008)
  • Author(s): Jia F, Mobarakeh JI, Dai H, Kato M, Xu A, Okuda T, Sakurai E, Okamura N, Takahashi K, Yanai K.
  • Journal Title: J Pharmacol Sci. 107 Pages: 167-174
  • NAID: 10024320914
  • Peer Reviewed
• [Journal Article] Effects of a sedative antihistamine, D-chlorpheniramine, on regional cerebral perfusion and performance during simulated car driving. (2008)
  • Author(s): Tashiro M, Sakurada Y, Mochizuki H, Horikawa E, Maruyama M, Okamura N, Watanuki S, Arai H, Itoh M, Yanai K.
  • Journal Title: Hum Psychopharmacol. 23 Pages: 139-150
  • Peer Reviewed
• [Journal Article] Imaging amyloid pathology in the living brain (2008)
  • Author(s): Okamura N, et.al.
  • Journal Title: Curr Med Imaging Rev 4 Pages: 56-62
  • Peer Reviewed
• [Journal Article] In vivo visualization of donepezil binding in the brain of patients with Alzheimer's disease (2008)
  • Author(s): Okamura N, et.al.
  • Journal Title: Br J Clin Pharmacol 65 Pages: 472-479
  • Peer Reviewed
• [Presentation] タウイメージング用プローブの開発状況 (2011)
  • Author(s): 岡村信行
  • Organizer: AD画像診断サブコミッティ
  • Place of Presentation: 東京
  • Year and Date: 2011-02-05
• [Presentation] 軽度認知障害の進行予後予測のための画像バイオマーカーの比較検討 (2010)
  • Author(s): 岡村信行、古川勝敏、藁谷正明、富田尚希、田代学、工藤幸司、荒井啓行、谷内一彦
  • Organizer: 第31回日本臨床薬理学会年会
  • Place of Presentation: 京都
  • Year and Date: 2010-12-01
• [Presentation] αシヌクレイノパチーにおける[^<11>C]BF-227PET 画像所見 (2010)
  • Author(s): 岡村信行、菊池昭夫、武田篤、古本祥三、田代学、船木善仁、工藤幸司、岩田錬、谷内一彦
  • Organizer: 第50回日本核医学会学術総会
  • Place of Presentation: 大宮
  • Year and Date: 2010-11-12
• [Presentation] Measurement of Vesicular Monoamine Transporter Type 2 Density in Parkinson's Disease and Dementia with Lewy Bodies with [^<18>F]AV-133 PET. (2010)
  • Author(s): Okamura N, Villemagne VL, Pejoska S, Mulligan RS, O'Keefe G, Jones G, Skovronsky D, Rowe CC.
  • Organizer: 第50回日本核医学会学術総会
  • Place of Presentation: 大宮
  • Year and Date: 2010-11-11
• [Presentation] 認知症の分子イメージング.シンポジウム9.イメージングによる精神・神経疾患研究の新しい展開 (2010)
  • Author(s): 岡村信行
  • Organizer: 第20回日本臨床精神神経薬理学会・第40回日本神経精神薬理学会 合同年会
  • Place of Presentation: 仙台
  • Year and Date: 2010-09-16
• [Presentation] 蛋白ミスフォールディングの分子イメージング (2010)
  • Author(s): 岡村信行
  • Organizer: 第8回脳核医学画像解析研究会
  • Place of Presentation: 東京
  • Year and Date: 2010-09-04
• [Presentation] Development of novel imaging probe for senile plaques and neurofibrillary tangles. (2010)
  • Author(s): Okamura N, Kudo Y.
  • Organizer: International Symposium for Molecular Imaging Educational Course of Tohoku University
  • Place of Presentation: Sendai
  • Year and Date: 2010-03-12
• [Presentation] Noninvasive detection of amyloid deposits using near-infrared fluorescence probe X50 in mice. (2010)
  • Author(s): Okamura N, Mori M, Furumoto S, Yanai K, Kudo Y.
  • Organizer: 2010 World Molecular Imaging Congress
  • Place of Presentation: Kyoto
• [Presentation] [^<11>C]BF-227 PET study of patients with protein misfolding diseases. (2009)
  • Author(s): Okamura N, Furumoto S, Tashiro M, Furukawa K, Arai H, Doh-ura K, Kudo Y, Yanai K.
  • Organizer: The 2009 International Symposium on Early Detection and Rehabilitation Technology of Dementia-DRD2009
  • Place of Presentation: Okayama
  • Year and Date: 2009-12-11
• [Presentation] 脳神経疾患におけるバイオマーカー (2009)
  • Author(s): 岡村信行、谷内一彦
  • Organizer: 第30回日本臨床薬理学会年会 ワークショップ1「臨床試験とバイオマーカー」
  • Place of Presentation: 横浜
  • Year and Date: 2009-12-03
• [Presentation] アミロイドイメージングプローブ[^<18>F]FACTのアルツハイマー病早期診断における有用性の検討 (2009)
  • Author(s): 岡村信行、古本祥三、田代学、古川勝敏、杉健太郎、荒井啓行、工藤幸司、谷内一彦
  • Organizer: 第16回東北脳循環カンファランス
  • Place of Presentation: 仙台
  • Year and Date: 2009-11-28
• [Presentation] アミロイドイメージングの現状と展望 (2009)
  • Author(s): 岡村信行
  • Organizer: 第18回東北老年期認知症研究会
  • Place of Presentation: 仙台
  • Year and Date: 2009-11-14
• [Presentation] 認知症の分子イメージング (2009)
  • Author(s): 岡村信行
  • Organizer: 第49回日本核医学会学術総会 シンポジウム「脳疾患における分子イメージング」
  • Place of Presentation: 旭川
  • Year and Date: 2009-10-01
• [Presentation] PETを用いたアルツハイマー病の超早期診断法の確立と普及について (2009)
  • Author(s): 岡村信行
  • Organizer: 第15回CYPRIS技術交流会
  • Place of Presentation: 東京
  • Year and Date: 2009-08-27
• [Presentation] Non-invasive detection of α-synuclein deposits in human brain using [^<11>C]BF227-PET. (2009)
  • Author(s): Okamura N, Kikuchi A, Takeda A, Furumoto S, Furukawa K, Arai H, Fodero-Tavoletti MT, Villemagne VL, Itoyama Y, Yanai K, Kudo Y.
  • Organizer: 2009 International Conference on Alzheimer's Disease (ICAD)
  • Place of Presentation: Vienna
  • Year and Date: 2009-07-15
• [Presentation] PETを用いた脳アミロイドの画像化 (2009)
  • Author(s): 岡村信行
  • Organizer: 第50回日本神経学会総会 シンポジウム「神経機能画像の進歩」
  • Place of Presentation: 仙台
  • Year and Date: 2009-05-22
• [Presentation] PETを用いた脳アミロイドの画像化 (2009)
  • Author(s): 岡村信行
  • Organizer: 第50回日本神経学会総会
  • Place of Presentation: 仙台国際センター(宮城県)
  • Year and Date: 2009-05-22
• [Presentation] [^<11>C]BF-227 PET Study in Protein Conformational Diseases. (2009)
  • Author(s): Okamura N, Furumoto S, Tashiro M, Funaki Y, Kikuchi A, Shiga Y, Furukawa K, Arai H, Doh-ura K, Iwata R, Yanai K, Kudo Y.
  • Organizer: EANM'09 Annual Congress of the European Association of Nuclear Medicine
  • Place of Presentation: Barcelona
• [Presentation] PET imaging of brain amyloid deposits using BF-227 and its derivative (2008)
  • Author(s): Okamura N, et.al.
  • Organizer: ICAD2008
  • Place of Presentation: Chicago, USA
  • Year and Date: 2008-07-28
• [Presentation] PET imaging of brain amyloid deposits using BF-227 and its derivative. (2008)
  • Author(s): Okamura N, Furumoto S, Furukawa K, Tashiro M, Kato M, Mori M, Iwata R, Yanai K, Arai H, Kudo Y.
  • Organizer: Alzheimer's Imaging Consortium Pre-conference
  • Place of Presentation: Chicago, USA
  • Year and Date: 2008-07-26
• [Presentation] In vivo imaging of brain amyloid deposits using BF-227 and its derivative (2008)
  • Author(s): Okamura N, et.al.
  • Organizer: SNM2008
  • Place of Presentation: New Orleans, USA
  • Year and Date: 2008-06-15
• [Presentation] Molecular PET imaging of acetylcholine esterase (AChE), histamine H1 receptor and amyloid deposits in Alzheimer disease. (2008)
  • Author(s): Okamura N, Yanai K.
  • Organizer: The 13th International Conference on Biomedical Engineering (ICBME2008)
  • Place of Presentation: Singapore
• [Presentation] PET imaging of brain amyloid deposits using BF-227 and its derivative. (2008)
  • Author(s): Okamura N, Furumoto S, Furukawa K, Tashiro M, Kato M, Mori M, Iwata R, Yanai K, Arai H, Kudo Y.
  • Organizer: Alzheimer's Association International Conference on Alzheimer's Disease 2008
  • Place of Presentation: Chicago, USA
• [Presentation] In vivo imaging of brain amyloid deposits using BF-227 and its derivative. (2008)
  • Author(s): Okamura N, Furumoto S, Tashiro M, Kato M, Funaki Y, Furukawa K, Arai H, Iwata R, Yanai K, Kudo Y.
  • Organizer: SNM 2008 Annual Meeting
  • Place of Presentation: New Orleans, USA
• [Remarks] ホームページ等
  • URL: http://www.miec.umin.jp/cgi-bin/gaiyo.cgi