In vivo activated glia imaging by development of novel peripheral benzodiazepine receptor ligands

• Project/Area Number: 20790047
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Single-year Grants
• Research Field: Physical pharmacy
• Research Institution: National Institute of Radiological Sciences
• Principal Investigator: MAEDA Jun National Institute of Radiological Sciences, 分子イメージング研究センター, 主任研究員 (30415426)
• Project Period (FY): 2008 – 2009
• Project Status: Completed (Fiscal Year 2009)
• Budget Amount: ¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000); Fiscal Year 2009: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000); Fiscal Year 2008: ¥3,120,000 (Direct Cost: ¥2,400,000、Indirect Cost: ¥720,000)
• Keywords: イメージング / 陽電子断層撮像(PET) / 末梢性ベンゾジアゼピン受容体 / アルツハイマー病 / 多発性硬化症 / 画像診断薬

Research Abstract

To visualize the neuroinflammation of human brain by positron emission tomography (PET), I synthesized novel PBR positron-labeled ligand [^<11>C]AC-5216 and its derivatives, and invested the profiles of these ligands. [^<11>C]AC-5216 is useful ligand for imaging of neuroinflammation in rodent brain. Since [^<11>C]AC-5216 had a lot of individual variation about brain uptake in human PET study, improvement of chemical structure was necessary for imaging of human neuroinflammation.

Research Products

• [Journal Article] In-vivo visualization of key molecular processes involved in Alzheimer's disease pathogenesis: Insights from neuroimaging research in humans and rodent models (2010)
  • Author(s): Higuchi M, Maeda J, Ji B, Maruyama M, Okauchi T, Tokunaga M, Ono M, Suhara T
  • Journal Title: Biochim Biophys Acta 1802(4) Pages: 373-388
  • Peer Reviewed
• [Journal Article] Development of N-[11C]methylamino 4-hydroxy-2(1H)-quinolone derivatives as PET radioligands for the glycine-binding site of NMDA receptors. (2009)
  • Author(s): Fuchigami T, Haradahira T, Fujimoto N, Nojiri Y, Mukai T, Yamamoto F, Okauchi T, Maeda J, Suzuki K, Suhara T, Yamaguchi H, Ogawa M, Magata Y, Maeda M.
  • Journal Title: Bioorg Med Chem 17(15) Pages: 5665-5675
  • Peer Reviewed
• [Journal Article] 遺伝子改変マウスを用いたイメージングバイオマーカーの評価 (2009)
  • Author(s): 前田純、樋口真人、須原哲也
  • Journal Title: 日本精神神経薬理学雑誌 29巻 Pages: 73-78
  • NAID: 10024900097
• [Journal Article] Quantitative analysis of peripheral benzodiazepine receptor in the human brain using PET with [11C]-AC-5216. (2009)
  • Author(s): Miyoshi M, Ito H, Arakawa R, Takahashi H, Takano H, Higuchi M, Okumura M, Otsuka T, Kodaka F, Sekine M, Sasaki T, Fujie S, Seki C, Maeda J, Nakao R, Zhang MR, Fukumura T, Matsumoto M, Suhara T.
  • Journal Title: J Nucl Med 50(7) Pages: 1095-1101
  • Peer Reviewed
• [Journal Article] Monkey brain activity modulated by reward preferences: a positron emission tomography study. (2009)
  • Author(s): Obayashi S, Nagai Y, Suhara T, Okauchi T, Inaji M, Iriki A, Maeda J.
  • Journal Title: Neurosci Res 64(4) Pages: 421-428
  • Peer Reviewed
• [Journal Article] Utility of small-animal positron emission tomographic imaging of rats for preclinical development of drugs acting on the serotonin transporter (2009)
  • Author(s): Saijo T, Maeda J, Okauchi T, Maeda JI, Morio Y, Kuwahara Y, Suzuki M, Goto N, Suzuki K, Higuchi M, Suhara T.
  • Journal Title: Int J Neuropsychopharmacol 23 Pages: 1-12
  • Peer Reviewed
• [Journal Article] Neuroimaging and physiological evidence for involvement of glutamatergic transmission in regulation of the striatal dopaminergic system (2009)
  • Author(s): Tokunaga M, Seneca N, Shin RM, Maeda J, Obayashi S, Okauchi T, Nagai Y, Zhang MR, Nakao R, Ito H, Innis RB, Halldin C, Suzuki K, Higuchi M, Suhara T.
  • Journal Title: J Neurosci 29(6) Pages: 1887-1896
  • Peer Reviewed
• [Journal Article] Neuroimaging and physiological evidence for involvement of glutamatergic transmission in regulation of the striatal dopaminergic system. (2009)
  • Author(s): Tokunaga M
  • Journal Title: J Neurosci 29 Pages: 1887-1896
  • Peer Reviewed
• [Journal Article] Utility of small-animal positron emission tomographic imaging of rats for preclinical development of drugs acting on the serotonin transporter. (2009)
  • Author(s): Saijo T
  • Journal Title: Int J Neuropsychopharmacol 12 Pages: 1021-1032
  • Peer Reviewed
• [Journal Article] Monkey brain activity modulated by reward preferences : a positron emission tomography study. (2009)
  • Author(s): Obayashi S
  • Journal Title: Neurosci Res 64 Pages: 421-428
  • Peer Reviewed
• [Journal Article] Quantitative analysis of peripheral benzodiazepine receptor in the human brain using PET with 11C-AC-5216. (2009)
  • Author(s): Miyoshi M
  • Journal Title: J Nucl Med 50 Pages: 1095-1101
  • Peer Reviewed
• [Journal Article] 遺伝子改変マウスを用いたイメージングバイオマーカーの評価 (2009)
  • Author(s): 前田純
  • Journal Title: 日本精神神経薬理学雑誌 29 Pages: 73-78
  • NAID: 10024900097
• [Journal Article] Development of N-[11C]methylamino 4-hydroxy-2(1H)-quinolone derivatives as PET radioligands for the glycine-binding site of NMDA receptors. (2009)
  • Author(s): Fuchigami T
  • Journal Title: Bioorg Med Chem 17 Pages: 5665-5675
  • Peer Reviewed
• [Journal Article] Imaging of peripheral benzodiazepine receptor expression as biomarkers of detrimental versus beneficial glial responses in mouse models of Alzheimer's and other CNS pathologies (2008)
  • Author(s): Ji B, Maeda J, Sawada M, Ono M, Okauchi T, Inaji M, Zhang MR, Suzuki K, Ando K, Staufenbiel M, Trojanowski JQ, Lee VM, Higuchi M, Suhara T.
  • Journal Title: J Neurosci 28(47) Pages: 12255-12267
  • Peer Reviewed
• [Journal Article] Alpha-CaMKII deficiency causes immature dentate gyrus, a novel candidate endophenotype of psychiatric disorders (2008)
  • Author(s): Yamasaki N, Maekawa M, Kobayashi K, Kajii Y, Maeda J, Soma M, Takao K, Tanda K, Ohira K, Toyama K, Kanzaki K, Fukunaga K, Sudo Y, Ichinose H, Ikeda M, Iwata N, Ozaki N, Suzuki H, Higuchi M, Suhara T, Yuasa S, Miyakawa T.
  • Journal Title: Mol Brain 1(1) Pages: 6-6
  • Peer Reviewed
• [Journal Article] Difference in brain distributions of carbon 11-labeled 4-hydroxy-2(1H)-quinolones as PET radioligands for the glycine-binding site of the NMDA ion channel (2008)
  • Author(s): Fuchigami T, Haradahira T, Fujimoto N, Okauchi T, Maeda J, Suzuki K, Suhara T, Yamamoto F, Sasaki S, Mukai T, Yamaguchi H, Ogawa M, Magata Y, Maeda M.
  • Journal Title: Nucl Med Biol 35(2) Pages: 203-212
  • Peer Reviewed
• [Journal Article] Neurobehavioral protection by single dose l-deprenyl against MPTP-induced parkinsonism in common marmosets (2008)
  • Author(s): Ando K, Maeda J, Inaji M, Okauchi T, Obayashi S, Higuchi M, Suhara T, Tanioka Y
  • Journal Title: Psychopharmacology 195(4) Pages: 509-516
  • Peer Reviewed
• [Journal Article] Neurobehavioral protection by single dose l-deprenyl against MPTP-induced parkinsonism in common marmosets. (2008)
  • Author(s): Ando K
  • Journal Title: Psychopharmacology 195 Pages: 509-516
  • Peer Reviewed
• [Journal Article] Difference in brain distributions of carbon 11-labeled 4-hydroxy-2(1H)-quinolones as PET radioligands for the glycine-binding site of the NMDA ion channel. (2008)
  • Author(s): Fuchigami T
  • Journal Title: Nucl. Med. Biol. 35 Pages: 203-212
  • Peer Reviewed
• [Journal Article] Alpha-CaMKII deficiency causes immature dentate gyrus, a novel candidate endophenotype of psychiatric disorders. (2008)
  • Author(s): Yamasaki N
  • Journal Title: Mol. Brain 1 Pages: 6-6
  • Peer Reviewed
• [Journal Article] Imaging of peripheral benzodiazepine receptor expression as biomarkers of detrimental versus beneficial glial responses in mouse models of Alzheimer's and other CNS patholoeies. (2008)
  • Author(s): Ji B
  • Journal Title: J. Neurosci. 28 Pages: 12255-12267
  • Peer Reviewed
• [Journal Article] アミロイドイメージングと新しい画像診断法の開発 (2008)
  • Author(s): 前田 純
  • Journal Title: 治療学 42 Pages: 58-62
• [Presentation] 小動物PETを用いたアルツハイマー病診断用PETリガンドの開発とその結合特性の解明 (2010)
  • Author(s): 前田純
  • Organizer: 分子イメージング研究シンポジウム
  • Place of Presentation: 東京
  • Year and Date: 2010-01-22
• [Presentation] 小動物PETを用いたアルツハイマー病診断用PETリガンドの開発とその結合特性の解明 (2010)
  • Author(s): 前田純
  • Organizer: 分子イメージング研究シンポジウム
  • Place of Presentation: 日経ホール
  • Year and Date: 2010-01-22
• [Presentation] 動物定量PETの現状-トランスジェニックマウスとマウス定量PET- (2008)
  • Author(s): 前田純
  • Organizer: 第48回日本核医学会総会
  • Place of Presentation: 千葉
  • Year and Date: 2008-10-25
• [Presentation] 小動物定量PETの現状-トランスジェニックマウスとマウス定量PET- (2008)
  • Author(s): 前田 純
  • Organizer: 第48回日本核医学会総会
  • Place of Presentation: 幕張メッセ
  • Year and Date: 2008-10-25
• [Presentation] 動物PETを用いたベンゾジアゼピン受容体PETリガンドの開発および評価 (2008)
  • Author(s): 前田純
  • Organizer: 第9回日本脳神経核医学研究会
  • Place of Presentation: 千葉
  • Year and Date: 2008-10-24
• [Presentation] 動物PETを用いたベンゾジアゼピン受容体PETリガンドの開発および評価 (2008)
  • Author(s): 前田 純
  • Organizer: 第9回日本脳神経核医学研究会
  • Place of Presentation: 幕張メッセ
  • Year and Date: 2008-10-24
• [Presentation] 遺伝子改変動物を用いたイメージングバイオマーカーの評価 (2008)
  • Author(s): 前田純
  • Organizer: 第18回日本臨床精神神経薬理学会/第38回日本精神神経薬理学会合同年会
  • Place of Presentation: 東京
  • Year and Date: 2008-10-01
• [Presentation] 遺伝子改変動物を用いたイメージングバイオマーカーの評価 (2008)
  • Author(s): 前田 純
  • Organizer: 第18回日本臨床精神神経薬理学会, 第38回日本精神神経薬理学会 合同年会
  • Place of Presentation: 品川プリンスホテルアネックスタワー
  • Year and Date: 2008-10-01
• [Presentation] ・-アミロイド産生マウスを用いた・-アミロイドリガンド[11C]PIBの結合機序の解明 (2008)
  • Author(s): 前田純
  • Organizer: 生体機能と創薬シンポジウム2008
  • Place of Presentation: 東京
  • Year and Date: 2008-09-05
• [Presentation] β-アミロイド産生マウスを用いたβ-アミロイドリガンド[^<11>C]PIBの結合機序の解明 (2008)
  • Author(s): 前田 純
  • Organizer: 生体機能と創薬シンポジウム 2008 東京
  • Place of Presentation: 星薬科大学
  • Year and Date: 2008-09-05
• [Presentation] 東京小動物PETを用いた遺伝子改変マウスの分子イメージング (2008)
  • Author(s): 前田純
  • Organizer: Neuroscience2008
  • Place of Presentation: 東京
  • Year and Date: 2008-07-11
• [Presentation] 小動物PETを用いた遺伝子改変マウスの分子イメージング (2008)
  • Author(s): 前田 純
  • Organizer: Neuroscience2008
  • Place of Presentation: 東京国際フォーラム
  • Year and Date: 2008-07-11
• [Remarks]
  • URL: http://www.nirs.go.jp/seika/brain/
• [Remarks]
  • URL: http://www.nirs.go.jp/seika/brain/
• [Remarks]
  • URL: http://www.nirs.go.jp/seika/brain/