Functional bioimaging of brain microglia by purine receptor PET ligands

• Project/Area Number: 22590053
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Physical pharmacy
• Research Institution: National Institute of Radiological Sciences
• Principal Investigator: MAEDA Jun 独立行政法人放射線医学総合研究所, 分子イメージング研究センター, 主任研究員 (30415426)
• Project Period (FY): 2010 – 2012
• Project Status: Completed (Fiscal Year 2012)
• Budget Amount: ¥4,550,000 (Direct Cost: ¥3,500,000、Indirect Cost: ¥1,050,000); Fiscal Year 2012: ¥910,000 (Direct Cost: ¥700,000、Indirect Cost: ¥210,000); Fiscal Year 2011: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000); Fiscal Year 2010: ¥2,600,000 (Direct Cost: ¥2,000,000、Indirect Cost: ¥600,000)
• Keywords: 陽電子撮像法 / P2Y12受容体 / アデノシンA2a受容体 / ミクログリア / アルツハイマー病 / 陽電子断層撮像法（PET） / プリン受容体 / アデノシン受容体 / 陽電子断層撮像法(PET)

Research Abstract

To visualize the microglial cells in the brain using positron emission tomography (PET), the development and preclinical evaluation of purinergic receptor PET ligands have been demonstrated. P2Y12 receptor ligand [11C]clopidogrel and adenosine A2a ligand [11C]TMSX have been investigated, however both ligands fail to detect the microglial cells in the brain.

Research Products

• [Journal Article] Molecular imaging of dementia (2012)
  • Author(s): Mori T, Maeda J, Shimada H, Higuchi M, Shinotoh H, Ueno S, Suhara T
  • Journal Title: Psychogeriatrics Volume: 12(2) Issue: 2 Pages: 106-114
  • DOI: 10.1111/j.1479-8301.2012.00409.x
  • NAID: 10029785231
  • Peer Reviewed
• [Journal Article] Mechanistic involvement of the calpain-calpastatin system in Alzheimer neuropathology (2012)
  • Author(s): Higuchi M, Iwata N, Matsuba Y, Takano J, Suemoto T, Maeda J, Ji B, Ono M, Staufenbiel M, Suhara T, Saido TC
  • Journal Title: FASEB J Volume: 26(3) Issue: 3 Pages: 1204-1217
  • DOI: 10.1096/fj.11-187740
  • Peer Reviewed
• [Journal Article] Imaging for metabotropic glutamate receptor subtype 1 in rat and monkey brains using PET with [18F]FITM (2012)
  • Author(s): Yamasaki T, Fujinaga M, Maeda J, Kawamura K, Yui J, Hatori A, Yoshida Y, Nagai Y, Tokunaga M, Higuchi M, Suhara T, Fukumura T, Zhang MR
  • Journal Title: Eur J Nucl Med Mol Imaging Volume: 39(4) Issue: 4 Pages: 632-641
  • DOI: 10.1007/s00259-011-1995-6
  • Peer Reviewed
• [Journal Article] PET Applications in Animal Models of Neurodegenerative and Neuroinflammatory Disorders (2012)
  • Author(s): Higuchi M, Maeda J, Ji B, Tokunaga M, Zhang MR, Maruyama M, Ono M, Fukumura T, Suhara T
  • Journal Title: Curr Top Behav Neurosci Volume: 11 Pages: 45-64
  • DOI: 10.1007/7854_2011_167
  • ISBN: 9783642287107, 9783642287114
  • Peer Reviewed
• [Journal Article] Characterization of 1-(2-[18F] fluoro-3-pyridyl)-4-(2-isopropyl-1-oxo- isoindoline-5-yl)-5-methyl-1H-1,2,3-triazole, a PET ligand for imaging the metabotropic glutamate receptor type 1 in rat and monkey brains (2012)
  • Author(s): Fujinaga M, Maeda J, Yui J, Hatori A, Yamasaki T, Kawamura K, Kumata K, Yoshida Y, Nagai Y, Higuchi M, Suhara T, Fukumura T, Zhang MR
  • Journal Title: J Neurochem Volume: 121(1) Issue: 1 Pages: 115-24
  • DOI: 10.1111/j.1471-4159.2011.07348.x
  • Peer Reviewed
• [Journal Article] Development of N-[4-[6-(isopropylamino)pyrimidin-4-yl]-1,3-thiazol-2-yl]-N-methyl-4-[11C]methylbenzamide for positron emission tomography imaging of metabotropic glutamate 1 receptor in monkey brain. (2012)
  • Author(s): Masayuki Fujinaga
  • Journal Title: J Med Chem Volume: 55 Issue: 24 Pages: 10042-10051
  • DOI: 10.1021/jm301597s
  • Peer Reviewed
• [Journal Article] (2011)
  • Author(s): 樋口 真人, 季 斌, 前田 純, 丸山 将浩, 小野 麻衣子, 澤田 誠, 須原 哲
  • Journal Title: アルツハイマー病とミクログリア臨床神経 Volume: 51 Pages: 1031-1031
• [Journal Article] Central nervous system drug evaluation using positron emission tomography (2011)
  • Author(s): Sekine M, Maeda J, Shimada H, Nogami T, Arakawa R, Takano H, Higuchi M, Ito H, Okubo Y, Suhara T
  • Journal Title: Clin Psychopharmacol Neurosci Volume: 9(1) Issue: 1 Pages: 9-16
  • DOI: 10.9758/cpn.2011.9.1.9
  • Peer Reviewed
• [Journal Article] In vivo positron emission tomographic imaging of glial responses to amyloid-beta and tau pathologies in mouse models of Alzheimer's disease and related disorders (2011)
  • Author(s): Maeda J, Zhang MR, Okauchi T, Ji B, Ono M, Hattori S, Kumata K, Iwata N, Saido TC, Trojanowski JQ, Lee VM, Staufenbiel M, Tomiyama T, Mori H, Fukumura T, Suhara T, Higuchi M
  • Journal Title: J Neurosci. Volume: 31(12) Issue: 12 Pages: 4720-4730
  • DOI: 10.1523/jneurosci.3076-10.2011
  • Peer Reviewed
• [Journal Article] In vivo and in vitro imaging of I_2 imidazoline receptors in the monkey brain (2011)
  • Author(s): Kawamura K, Maeda J, Hatori A, Okauchi T, Nagai Y, Higuchi M, Suhara T, Fukumura T, Zhang MR
  • Journal Title: Synapse Volume: 65(5) Issue: 5 Pages: 452-455
  • DOI: 10.1002/syn.20897
  • Peer Reviewed
• [Journal Article] In Vivo Positron Emission Tomographic Imaging of Glial Responses to Amyloid-{beta} and Tau Pathologies in Mouse Models of Alzheimer's Disease and Related Disorders. (2011)
  • Author(s): Maeda J
  • Journal Title: J Neurosci. Volume: 31 Pages: 4720-4730
• [Journal Article] Design, synthesis, radiolabeling, and in vivo evaluation of carbon-11 labeled N-[2-[4-(3-cyanopyridin-2-yl)piperazin-1-yl]ethyl]-3-methoxybenzamide (2010)
  • Author(s): Lacivita E, De Giorgio P, Lee IT, Rodeheaver SI, Weiss BA, Fracasso C, Caccia S, Berardi F, Perrone R, Zhang MR, Maeda J, Higuchi M, Suhara T, Schetz JA, Leopoldo M
  • Journal Title: a potential positron emission tomography tracer for the dopamine D4 receptors Volume: 53(20) Issue: 20 Pages: 7344-7355
  • DOI: 10.1021/jm100925m
  • Peer Reviewed
• [Journal Article] Glial cell-mediated deterioration and repair of the nervous system after traumatic brain injury in a rat model as assessed by positron emission tomography (2010)
  • Author(s): Yu I, Inaji M, Maeda J, Okauchi T, Nariai T, Ohno K, Higuchi M, Suhara T
  • Journal Title: J Neurotrauma Volume: 27(8) Issue: 8 Pages: 1463-1475
  • DOI: 10.1089/neu.2009.1196
  • Peer Reviewed
• [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
  • Journal Title: Biochim Biophys Acta. Volume: 1802 Pages: 373-388
• [Journal Article] Positron emission tomography measurement of dopamine D_2 receptoroccupancy in the pituitary and cerebral cortex : relation toantipsychotic-induced hyperprolactinemia. (2010)
  • Author(s): Arakawa R
  • Journal Title: J Clin Psychiatry Volume: 71 Pages: 1131-1137
• [Journal Article] Quantitative analysis of dopamine transporters in human brain using[^<11>C]PE2I and positron emission tomography : evaluation of reference tissue models. (2010)
  • Author(s): Seki C
  • Journal Title: Ann Nucl Med Volume: 24 Pages: 249-260
• [Journal Article] Glial cell-mediated deterioration and repair of the nervous system after traumatic brain injury in a rat model as assessed by positron emission tomography. (2010)
  • Author(s): Yu I
  • Journal Title: J Neurotrauma. Volume: 27 Pages: 1463-1475
• [Journal Article] Design, synthesis, radiolabeling, and in vivo evaluation of carbon-11 labeledN-[2-[4-(3-cyanopyridin-2-yl)piperazin-1-yl]ethyl]-3-methoxybenzamide, apotential positron emission tomography tracer for the dopamine D(4) receptors. (2010)
  • Author(s): Lacivita E
  • Journal Title: J Med Chem. Volume: 53 Pages: 7344-7355
• [Presentation] Altered serotonin release and serotonin 1A receptor density in CaMKIIα-deficient mice assessed by a comparison of in vivo PET and in vitro autoradiographic data (2012)
  • Author(s): Jun Maeda, Masaki Tokunaga, Ming-Rong Zhang, Takeharu Minamihisamatsu, Toshimitsu Fukumura, Tsuyoshi Miyakawa, Tetsuya Suhara, Makoto Higuchi
  • Organizer: Neuroreceptor Mapping 2012
  • Place of Presentation: Baltimore, USA
  • Year and Date: 2012-08-08
• [Presentation] PET Imaging of glial activation and neuroinflammation in dementia and other neurological disorders by translocator protein (TSPO) ligands (2012)
  • Author(s): Jun Maeda
  • Organizer: 14th Mind Brain Conference
  • Place of Presentation: Hamamatsu
  • Year and Date: 2012-02-15
• [Presentation] PET Imaging of glial activation and neuroinflammation in dementia and other neurological disorders by translocator protein (TSPO) ligands (2012)
  • Author(s): 前田純
  • Organizer: 14th Mind Brain Conference
  • Place of Presentation: ホテルクラウンパレス(浜松市)
  • Year and Date: 2012-02-15
• [Presentation] Altered serotonin release and serotonin 1A receptor density in CaMKII-alpha deficient mice assessed by a comparison of in vivo PET and in vitro autoradiographic data (2012)
  • Author(s): Jun Maeda
  • Organizer: Neuroreceptor Mapping 2012
  • Place of Presentation: Baltimore, United States of America
• [Presentation] 小動物PETによる認知症モデルマウスのイメージング (2011)
  • Author(s): 前田純
  • Organizer: 第6回分子イメージング学会
  • Place of Presentation: 神戸
  • Year and Date: 2011-05-27
• [Presentation] 小動物PETによる認知症モデルマウスのイメージング (2011)
  • Author(s): 前田純
  • Organizer: 第6回分子イメージング学会
  • Place of Presentation: 神戸国際会議場(神戸市)
  • Year and Date: 2011-05-27
• [Presentation] In vivo evaluation of a 18kDa translocator protein (TSPO/PBR) ligand [11C]AC-5216 in Alzheimer's disease mouse models (2010)
  • Author(s): Jun Maeda, Ming-Rong Zhang, Bin Ji, Takashi Okauchi, Toshimitsu Fukumura, Tetsuya Suhara, Makoto Higuchi
  • Organizer: World Molecular Imaging Congress 2010
  • Place of Presentation: Kyoto
  • Year and Date: 2010-09-11
• [Presentation] In vivo evaluation of a 18kDa translocator protein (TSPO/PBR) ligand [^<11>C]AC-5216 in Alzheimer's disease mouse models (2010)
  • Author(s): Maeda J
  • Organizer: World Molecular Imaging Congress 2010
  • Place of Presentation: 京都
  • Year and Date: 2010-09-11
• [Book] 認知症モデルマウスのイメージング,PET journal No.15 (2011)
  • Author(s): 前田純
  • Publisher: 先端医療技術研究所
• [Book] 物質依存の神経画像-PETを用いた研究,専門医のための精神科臨床リュミエール 26巻 依存症・衝動制御障害の治療 (2011)
  • Author(s): 前田純,須原哲也
  • Publisher: 中山書店
• [Book] 専門医のための精神科臨床リュミエール26依存性・衝動制御障害の治療 (2011)
  • Author(s): 前田純, 須原哲也
  • Total Pages: 9
  • Publisher: 中山書店
• [Remarks]
  • URL: http://www.nirs.go.jp/seika/brain/
• [Remarks] 分子神経イメージング研究プログラム
  • URL: http://www.nirs.go.jp/seika/brain/
• [Remarks]
  • URL: http://www.nirs.go.jp/seika/brain/brain/index.html
• [Remarks]
  • URL: http://www.nirs.go.jp/seika/brain/brain/index.html