Development of molecular imaging probes for β-amyloid and tau in Alzheimer's disease

• Project/Area Number: 20689023
• Research Category: Grant-in-Aid for Young Scientists (A)
• Allocation Type: Single-year Grants
• Research Field: Radiation science
• Research Institution: Kyoto University
• Principal Investigator: ONO Masahiro Kyoto University, 薬学研究科, 准教授 (80336180)
• Project Period (FY): 2008 – 2010
• Project Status: Completed (Fiscal Year 2010)
• Budget Amount: ¥24,570,000 (Direct Cost: ¥18,900,000、Indirect Cost: ¥5,670,000); Fiscal Year 2010: ¥6,890,000 (Direct Cost: ¥5,300,000、Indirect Cost: ¥1,590,000); Fiscal Year 2009: ¥7,280,000 (Direct Cost: ¥5,600,000、Indirect Cost: ¥1,680,000); Fiscal Year 2008: ¥10,400,000 (Direct Cost: ¥8,000,000、Indirect Cost: ¥2,400,000)
• Keywords: 放射性医薬品 / 造影剤 / アルツハイマー病 / アミロイドβ / タウ / PET / SPECT / イメージング / 診断 / βアミロイド / 分子イメージング

Research Abstract

Alzheimer's disease (AD) is a neurodegenerative disease of the brain associated with irreversible cognitive decline, memory impairment, and behavioral changes. Postmortem brains of AD patients reveal neuropathologic features : the presence of senile plaques (SPs) and neurofibrillary tangles (NFTs), which contain β-amyloid proteins and highly phosphorylated tau proteins. In the present study, we successfully designed and synthesized several PET/SPECT imaging probes for in vivo detection of SPs and NFTs, and evaluated their utility as molecular imaging probes for SPs and NFTs.

Research Products

• [Journal Article] Diphenylpropynone derivatives as probes for imaging β-amyloid plaques. (2011)
  • Author(s): Ono M, Watanabe H, Watanabe R, Haratake M, Nakayama M, Saji H.
  • Journal Title: Bioorganic & Medicinal Chemistry 21 Pages: 117-120
  • Peer Reviewed
• [Journal Article] Synthesis and biological evaluation of indole-chalcone derivatives as β-amyloid imaging probe. (2011)
  • Author(s): Cui M, Ono M, Kimura H, Liu BL, Saji H
  • Journal Title: Bioorganic & Medicinal Chemistry Letters 21 Pages: 980-982
  • Peer Reviewed
• [Journal Article] Diphenylpropynone derivatives as probes for imaging β-amyloid plaques (2011)
  • Author(s): Ono M, Watanabe H, Watanabe R, Haratake M, Nakayama M, Saji H
  • Journal Title: Bioorganic & Medicinal Chemistry Letters Volume: 21 Pages: 117-120
  • Peer Reviewed
• [Journal Article] Synthesis and biological evaluation of indole-chalcone derivatives as β-amyloid imaging probe (2011)
  • Author(s): Cui M, Ono M, Kimura H, Liu BL, Saji H
  • Journal Title: Bioorganic & Medicinal Chemistry Letters Volume: 21 Pages: 980-982
  • Peer Reviewed
• [Journal Article] ^<99m>Tc/Re complexes based on flavone and aurone as SPECT probes for imaging cerebral β-amyloid plaques. (2010)
  • Author(s): Ono M, Ikeoka R, Watanabe H, Kimura H, Fuchigami T, Haratake M, Saji H, Nakayama M.
  • Journal Title: Bioorganic & Medicinal Chemistry Letters 20 Pages: 5742-5748
  • NAID: 120006984924
  • Peer Reviewed
• [Journal Article] Novel benzofurans with ^<99m>Tc complexes as probes for imaging cerebral β-amyloid plaques using single photon emission computed tomography. (2010)
  • Author(s): Ono M, Fuchi Y, Fuchigami T, Kobashi N, Kimura H, Haratake M, Saji H, Nakayama M.
  • Journal Title: ACS Medicinal Chemistry 1 Pages: 443-447
  • Peer Reviewed
• [Journal Article] Fluorinated benzofuran derivatives for PET imaging of β-amyloid plaques in Alzheimer's disease brains. (2010)
  • Author(s): Cheng Y, Ono M, Kimura H, Kagawa S, Nishii R, Kawashima H, Saji H.
  • Journal Title: ACS Medicinal Chemistry Letters 1 Pages: 321-325
  • Peer Reviewed
• [Journal Article] Synthesis and evaluation of novel chalcone derivatives with ^<99m>Tc/Re complexes as potential probes for detection of β-amyloid plaques. (2010)
  • Author(s): Ono M, Ikeoka R, Watanabe H, Kimura H, Fuchigami T, Haratake M, Saji H, Nakayama M.
  • Journal Title: ACS Chemical Neuroscience 1 Pages: 598-607
  • Peer Reviewed
• [Journal Article] Synthesis and characterization of novel phenylindoles as potential probes for imaging of β-amyloid plaques in the brain. (2010)
  • Author(s): Watanabe H, Ono M, Haratake M, Kobashi N, Saji H, Nakayama M.
  • Journal Title: Bioorganic & Medicinal Chemistry 18 Pages: 4740-4746
  • Peer Reviewed
• [Journal Article] Synthesis and characterization of novel phenylindoles as potential probes for imaging of β-amyloid plaques in the brain (2010)
  • Author(s): Watanabe H, Ono M, Haratake M, Kobashi N, Saji H, Nakayama M
  • Journal Title: Bioorganic & Medicinal Chemistry Volume: 18 Pages: 4740-4746
  • Peer Reviewed
• [Journal Article] Synthesis and evaluation of novel chalcone derivatives with ^<99m>Tc/Re complexes as potential probes for detection of β-amyloid plaques (2010)
  • Author(s): Ono M, Ikeoka R, Watanabe H, Kimura H, Fuchigami T, Haratake M, Saji H, Nakayama M
  • Journal Title: ACS Chemical Neuroscience Volume: 1 Pages: 598-607
  • Peer Reviewed
• [Journal Article] Fluorinated benzofuran derivatives for PET imaging of β-amyloid plaques in Alzheimer's disease brains (2010)
  • Author(s): Cheng Y, Ono M, Kimura H, Kagawa S, Nishii R, Kawashima H, Saji H
  • Journal Title: ACS Medicinal Chemistry Letters Volume: 1 Pages: 321-325
  • Peer Reviewed
• [Journal Article] Novel benzofurans with ^<99m>Tc complexes as probes for imaging cerebral β-amyloid plaques using single photon emission computed tomography (2010)
  • Author(s): Ono M, Fuchi Y, Fuchigami T, Kobashi N, Kimura H, Haratake M, Saji H, Nakayama M
  • Journal Title: ACS Medicinal Chemistry Letters Volume: 1 Pages: 443-447
  • Peer Reviewed
• [Journal Article] ^<99m>Tc/Re complexes based on flavone and aurone as SPECT probes for imaging cerebral β-amyloid plaques (2010)
  • Author(s): Ono M, Ikeoka R, Watanabe H, Kimura H, Fuchigami T, Haratake M, Saji H, Nakayama M
  • Journal Title: Bioorganic & Medicinal Chemistry Letters Volume: 20 Pages: 5742-5748
  • NAID: 120006984924
  • Peer Reviewed
• [Journal Article] Development of positron-emission tomography /single-photon emission computed tomography imaging probes for in vivo detection of β-amyloid plaques in Alzheimer's brains. (2009)
  • Author(s): Ono M.
  • Journal Title: Chemical & Pharmaceutical Bulletin 57 Pages: 1029-1039
  • Peer Reviewed
• [Journal Article] Molecular imaging by PET/SPECT. (2009)
  • Author(s): Ono M.
  • Journal Title: Yakugaku Zasshi 129 Pages: 279-287
  • NAID: 110007123176
  • Peer Reviewed
• [Journal Article] ^<18>F-labeled flavones for in vivo imaging of β-amyloid plaques in Alzheimer's brains. (2009)
  • Author(s): Ono M, Watanabe R, Kawashima H, Kawai T, Watanabe H, Haratake M, Saji H, Nakayama M.
  • Journal Title: Bioorganic and Medicinal Chemistry 17 Pages: 2009-2076
  • Peer Reviewed
• [Journal Article] Synthesis and biological evaluation of radioiodinated 2,5-diphenyl-1,3,4-oxadiazoles for detecting β-amyloid plaques in the brain. (2009)
  • Author(s): Watanabe H, Ono M, Ikeoka R, Haratake M, Saji H, Nakayama M.
  • Journal Title: Bioorganic and Medicinal Chemistry 17 Pages: 6402-6406
  • Peer Reviewed
• [Journal Article] Fluoro-pegylated chalcones as positron emission tomography probes for in vivo imaging of β-amyloid plaques in Alzheimer's disease. (2009)
  • Author(s): Ono M, Watanabe R, Kawashima H, Cheng Y, Kimura H, Watanabe H, Haratake M, Saji H, Nakayama M.
  • Journal Title: Journal of Medicinal Chemistry 52 Pages: 6394-6401
  • Peer Reviewed
• [Journal Article] Fluoro-pegylated chalcones as poitron emission tomography probes for in vivo imaging of β-amyloid plaques in Alzheimer's b (2009)
  • Author(s): Ono M, et al.
  • Journal Title: Journal of Medicinal Chemistry 52 Pages: 6394-6401
  • Peer Reviewed
• [Journal Article] Push-pull benzothiazole derivatives as probes for detecting ss-amyloid plaques in Alzheimer's brains. (2009)
  • Author(s): Ono M, et al.
  • Journal Title: Bioorganic and Medicinal Chemistry 17 Pages: 6402-6406
  • Peer Reviewed
• [Journal Article] 18F-labeled flavones for in vivo imaging of ss-amyloid plaques in Alzheimer's brains (2009)
  • Author(s): Ono M, et al.
  • Journal Title: Bioorganic and Medicinal Chemistry 17 Pages: 2069-2076
  • Peer Reviewed
• [Journal Article] Novel radioiodinated aurones as probes for SPECT imaging of beta-amyloid plaques in the brain (2009)
  • Author(s): Maya Y, Ono M, Watanabe H, et.al.
  • Journal Title: Bioconjugate Chem 20 Pages: 95-101
  • Peer Reviewed
• [Journal Article] 18F-labeled flavones for in vivo imaging of beta-amyloid plaques in Alzheimer's disease (2009)
  • Author(s): Ono M, Watanabe R, Kawashima H, et.al.
  • Journal Title: Bioorg Med Chem 17 Pages: 2069-76
  • Peer Reviewed
• [Journal Article] Molecular imaging by PET/SPECT (2009)
  • Author(s): Ono M
  • Journal Title: Yakugaku Zasshi 129 Pages: 279-287
  • NAID: 110007123176
  • Peer Reviewed
• [Journal Article] SPECT imaging agents for detecting cerebral β-amyloid plaques.
  • Author(s): Ono M, Saji H.
  • Journal Title: International Journal of Molecular Imaging in press
  • Peer Reviewed
• [Journal Article] Phenyldiazenyl benzothiazole derivatives as probes for in vivo imaging of neurofibrillary tangles in Alzheimer's disease brains.
  • Author(s): Matsumura K, Ono M, Hayashi S, Kimura H, Okamoto Y, Ihara M, Takahashi R, Mori H, Saji H.
  • Journal Title: Medicinal Chemistry Communications in press
  • Peer Reviewed
• [Journal Article] Synthesis and structure-affinity relationships of novel dibenzylideneacetone derivatives as probes for β-amyloid plaques.Journal of Medicinal Chemistry
  • Author(s): Cui MC, Ono M, Kimura H, Liu BL, Saji H.
  • Journal Title: (in press)
  • Peer Reviewed
• [Journal Article] Novel ^<18>F-labeled benzofuran derivatives with improved properties for PET imaging of ￡]-amyloid plaques in Alzheimer's brains.
  • Author(s): Ono M, Cheng Y, Kimura H, Cui MC, Kagawa S, Nishii R, Saji H.
  • Journal Title: Journal of Medicinal Chemistry in press
  • Peer Reviewed
• [Journal Article] Rhodanine and thiohydantoin derivatives for detecting tau pathology in Alzheimer's brains.
  • Author(s): Ono M, Hayashi S, Matsumura K, Kimura H, Okamoto Y, Ihara M, Takahashi R, Mori H, Saji H.
  • Journal Title: ACS Chemical Neuroscience in press
  • Peer Reviewed
• [Journal Article] Radioiodinated Benzimidazole Derivatives as Single Photon Emission Computed Tomography Probes for Imaging of β-Amyloid Plaques in Alzheimer's Disease
  • Author(s): Cui M, Ono M, Kimura H, Kawashima H, Liu BL, Saji H.
  • Journal Title: Nuclear Medicine and Biology in press
  • Peer Reviewed
• [Presentation] タウ結合性化合物の探索とその分子イメージングプローブへの応用 (2011)
  • Author(s): 松村憲志、小野正博、林瞬、木村寛之、岡本洋子、猪原匡史、高橋良輔、佐治英郎
  • Organizer: 第131回日本薬学会
  • Place of Presentation: 静岡
  • Year and Date: 2011-03-30
• [Presentation] Auroneを母核とする新規^<18>F標識Aβイメージングプローブの開発 (2011)
  • Author(s): 程妍、小野正博、木村寛之、上田真史、中本裕士、富樫かおり、中山守雄、佐治英郎
  • Organizer: 第131回日本薬学会
  • Place of Presentation: 静岡
  • Year and Date: 2011-03-30
• [Presentation] タウ結合性化合物の探索とその分子イメージングプローブへの応用 (2011)
  • Author(s): 松村憲志、小野正博、林瞬、木村寛之、岡本洋子、猪原匡史、高橋良輔、佐治英郎
  • Organizer: 第131年会日本薬学会
  • Place of Presentation: 静岡コンベンションアーツセンター(静岡)
  • Year and Date: 2011-03-30
• [Presentation] Auroneを母核とする新規^<18>F標識Aβイメージングプローブの開発 (2011)
  • Author(s): 程妍、小野正博、木村寛之、上田真史、中本裕士、富樫かおり、中山守雄、佐治英郎
  • Organizer: 第131年会日本薬学会
  • Place of Presentation: 静岡コンベンションアーツセンター(静岡)
  • Year and Date: 2011-03-30
• [Presentation] タウ結合性化合物の探索とその分子イメージングプローブへの応用 (2010)
  • Author(s): 松村憲志、小野正博、林瞬、木村寛之、岡本洋子、猪原匡史、高橋良輔、佐治英郎
  • Organizer: 第29回メディシナルケミストリーシンポジウム
  • Place of Presentation: 京都
  • Year and Date: 2010-11-17
• [Presentation] タウ結合性化合物の探索とその分子イメージングプローブへの応用 (2010)
  • Author(s): 松村憲志、小野正博、林瞬、木村寛之、岡本洋子、猪原匡史、高橋良輔、佐治英郎
  • Organizer: 第29回メディシナルケミストリーシンポジウム
  • Place of Presentation: 京都テルサ 京都府民総合交流プラザ(京都)
  • Year and Date: 2010-11-17
• [Presentation] ^<18>F Labeled Benzofuran Derivatives as PET Probes for Detection of β-Amyloid Plaques (2010)
  • Author(s): 程妍、小野正博、木村寛之、加川信也、西井龍一、佐治英郎
  • Organizer: 第50回日本核医学会
  • Place of Presentation: 大宮
  • Year and Date: 2010-11-11
• [Presentation] アルツハイマー病診断を目的とした新規タウイメージングプローブの開発 (2010)
  • Author(s): 松村憲志、小野正博、林瞬、木村寛之、岡本洋子、猪原匡史、高橋良輔、佐治英郎
  • Organizer: 第50回日本核医学会
  • Place of Presentation: 大宮
  • Year and Date: 2010-11-11
• [Presentation] ^<18>F Labeled Benzofuran Derivatives as PET Probes for Detection of β-Amyloid Plaques (2010)
  • Author(s): 程妍、小野正博、木村寛之、加川信也、西井龍一、佐治英郎
  • Organizer: 第50回核医学会
  • Place of Presentation: 大宮ソニックシティ(大宮)
  • Year and Date: 2010-11-11
• [Presentation] アルツハイマー病診断を目的とした新規タウイメージングプローブの開発 (2010)
  • Author(s): 林瞬、小野正博、松村憲志、木村寛之、河嶋秀和、佐治英郎
  • Organizer: 第50回核医学会
  • Place of Presentation: 大宮ソニックシティ(大宮)
  • Year and Date: 2010-11-11
• [Presentation] Fluorinated Benzofuran Derivatives for PET Imaging of β-Amyloid Plaques in Alzheimer's Disease Brains (2010)
  • Author(s): Yan Cheng, Masahiro Ono, Hiroyuki Kimura, Shinya Kagawa, Ryuichi Nishii, Hidekazu Kawashima, Hideo Saji
  • Organizer: World Molecular Imaging Congress
  • Place of Presentation: 京都
  • Year and Date: 2010-09-09
• [Presentation] Fluorinated Benzofuran Derivatives for PET Imaging of β-Amyloid Plaques in Alzheimer's Disease Brains (2010)
  • Author(s): Yan Cheng, Masahiro Ono, Hiroyuki Kimura, Shinya Kagawa, Ryuichi Nishii, Hidekazu Kawashima, Hideo Saji
  • Organizer: World Molecular Imaging Congress
  • Place of Presentation: 京都国際会館(京都)
  • Year and Date: 2010-09-09
• [Presentation] βアミロイドのPET/SPECT分子イメージングプローブの開発(次世代の薬効評価系を目指した新しい光学技術) (2010)
  • Author(s): 小野正博
  • Organizer: 日本薬理学会
  • Place of Presentation: 大阪
  • Year and Date: 2010-03-18
• [Presentation] βアミロイドの分子イメージングを目的としたPET/SPECTプローブの開発 (2010)
  • Author(s): 小野正博
  • Organizer: 日本薬理学会
  • Place of Presentation: 大阪
  • Year and Date: 2010-03-18
• [Presentation] アミロイドイメージングの基礎 (2009)
  • Author(s): 小野正博
  • Organizer: 第49回日本核医学会
  • Place of Presentation: 旭川
  • Year and Date: 2009-10-02
• [Remarks] ホームページ等
  • URL: http://www.pharm.kyoto-u.ac.jp/byotai/
• [Patent(Industrial Property Rights)] コンフォメーション病診断用組成物 (2010)
  • Inventor(s): 佐治英郎、小野正博
  • Industrial Property Rights Holder: 京都大学
  • Filing Date: 2010-04-12
  • Overseas
• [Patent(Industrial Property Rights)] コンフォメーション病診断用組成物 (2009)
  • Inventor(s): 佐治英郎、小野正博
  • Industrial Property Rights Holder: 京都大学
  • Industrial Property Number: 2009-107457
  • Filing Date: 2009-04-27
• [Patent(Industrial Property Rights)] コンフォメーション病診断用組成物 (2009)
  • Inventor(s): 佐治英郎、小野正博
  • Industrial Property Rights Holder: 京都大学
  • Industrial Property Number: 2009-222156
  • Filing Date: 2009-09-28
• [Patent(Industrial Property Rights)] コンフォメーション病診断のための組成物 (2009)
  • Inventor(s): 佐治英郎、小野正博
  • Industrial Property Rights Holder: 京都大学
  • Industrial Property Number: 2009-107457
  • Filing Date: 2009-04-27