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Quantitative analysis of dopaminergic synaptic function in human brain.

Research Project

Project/Area Number 09470198
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypeSingle-year Grants
Section一般
Research Field Radiation science
Research InstitutionFukui Medical University

Principal Investigator

YONEKURA Yoshiharu  Fukui Medical University, Biomedical Imaging Research Center, Professor, 高エネルギー医学研究センター, 教授 (60135572)

Co-Investigator(Kenkyū-buntansha) TSUCHIDA Tatsuro  Fukui Medical University, Dept. of Radiology, Instructor, 医学部・附属病院, 助手 (70303386)
MURATA Tetsuhito  Fukui Medical University, Dept. of Psychiatry, Instructor, 医学部, 助手 (80200294)
YASUHISA Fujibayashi  Fukui Medical University, Biomedical Imaging Research Center, Professor, 高エネルギー医学研究センター, 教授 (50165411)
定藤 規弘  福井医科大学, 高エネルギー医学研究センター, 講師 (00273003)
Project Period (FY) 1997 – 1999
Project Status Completed (Fiscal Year 1999)
Budget Amount *help
¥13,100,000 (Direct Cost: ¥13,100,000)
Fiscal Year 1999: ¥3,600,000 (Direct Cost: ¥3,600,000)
Fiscal Year 1998: ¥3,200,000 (Direct Cost: ¥3,200,000)
Fiscal Year 1997: ¥6,300,000 (Direct Cost: ¥6,300,000)
Keywordsdopamine / synaptic function / functional neuroimaging / PET / SPECT
Research Abstract

The aim of this study was to establish the methods for the quantitative analysis of dopaminergic synaptic function in human brain, basic an clinical sdudies were performed with various approach, including the kinetc analysis of SPECT imaging and basic experiments using fresh brain slices of rats. Serial dynamic SPECT imaging of I-123 iodobenzofuran (IBF) with intermittent arterial blood sampling permits to obtain binding potential of dopamine D2 receptors. In addition to the compartment analysis and simple target to nontarget ratio approach, we have developed a new graphical method which provides more reliable parameters on receptor binding. Dopamine transporter imaging was performed with I-123 fluoropropyl analogue of beta-CIT (FPCIT). FPCIT has an advantage of faster kinetics than beta-CIT, and test anr re-test brain SPECT scans demonstrated an excellent reproducibility of measuring the distribution volume in the striatum, suggesting that this tracer is promising for the clinical use. We also developed a system called dynamic positron autoradiography technique (dPAT) for serial imaging of fresh brain slices of rats with positron labeled radioligands. This new method permits the assessment of regional changes of radioactivity for several hours, and can be used to monitor glucose metabolism and receptor binding with various interventions, such as hypoxia and drug effects. It will play an important role in understanding the kinetic behaviour of radioligands.

Report

(4 results)
  • 1999 Annual Research Report   Final Research Report Summary
  • 1998 Annual Research Report
  • 1997 Annual Research Report
  • Research Products

    (32 results)

All Other

All Publications (32 results)

  • [Publications] Shigeru Yoshida: "The effects of neuronal perturbation on the uptake of [^<18>F]2-fluoro-2-deoxy-D-gulucose in brain slices of the rat"Neurosci. Res.. 154巻・3号. 271-278 (1998)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Tetsuhito Murata: "Dynamic changes in glucose metabolism by lactate loading as revealed by a positron autoradiographic technique using rat brain slices"Neurosci. Lett.. 24巻・2-3号. 155-158 (1998)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Tetsuhito Murata: "Triazolam-induced modulation of muscarinic acetylcholine receptor in living brain slices as revealed by a new positron-based imaging technique"J. Neural Transmn.. 105巻・10-12号. 1117-1127 (1998)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] 米倉 義晴: "ドパミンD_2受容体イメージング剤^<123>I-IBFの第1相臨床試験(第1報)―体内薬物動態及び吸収線量の検討―"核医学. 36巻・2号. 145-153 (1999)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] 米倉 義晴: "ドパミンD_2受容体イメージング剤^<123>I-IBFの第1相臨床試験(第2報)―脳内薬物動態及びその定量法の検討―"核医学. 36巻・2号. 155-168 (1999)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] 松本博樹: "^<123>I-IBFのヒトにおける代謝に関する検討"核医学. 36巻・2号. 169-177 (1999)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Tetsuhito Murata: "Dynamic changes in glucose metabolism induced by thiamine deficiency and its replenishment as revealed by a positron autoradiography technique using rat living brain slices"J. Neuro. Sci.. 106巻・1号. 29-36 (1999)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Tetsuhito Murata: "Dynamic changes in glucose metabolism of living rat brain slices induced by hypoxia and neurotoxic chemical-loading revealed by a positron autoradiography"J. Neural Transm.. 106巻・11-12号. 1075-1087 (1999)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Naoto Omata: "Hypoxic but not ischemic neurotoxicity due to free radicals as revealed by dynamic changes in glucose metabolism of living rat brain slices with a positron autoradiography technique"J. Cereb. Blood Flow metab.. 20巻・2号. 35-358 (2000)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Yoshida S, Murata T, Omata N, Wakin A, Fujibayashi Y, Isaki K, Oka H, Yonekura Y,: "The effects of neuronal perturbation on the uptake of [ィイD118ィエD1F]2-fluoro-2-deoxy-D-glucose in brain slices of the rat."Neurosci. Res.. 154(3). 271-278 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Murata T, Waki A, Omata N, Fujibayashi Y, Sadato N, Yano R, Yoshimoto M, Isaki K, Yonekura Y: "Dynamic changes in glucose metabolism by lactate slices."Neurosci. Lett.. 249(2-3). 420-426 (1995)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Murata T, Matsumura K, Sihver S, Onoe H, Bergstrom M, Sihver W, Yonekura Y, Langstrom B, Watanabe Y: "Triazolam-induced modulation of muscarinic acetylcholine receptor in living brain slices as revealed by a new positron-based imaging technique."J. Neural Transm.. 105(10-12). 1117-1127 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Yonekura Y, Sadato N, Tsuchida T, Uematsu H, Nakamura S, Yamamoto K, Ishii Y: "Phase 1 clinical study of ィイD1123ィエD1I-IBF, a new radioligand for evaluating dopamine DィイD22ィエD2 receptor with SPECT (I); biodistribution and dosimetry."Kakuigaku (Jpn. J. Nucl. Med.). 36(2). 145-153 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Yonekura Y, Sadato N, Tsuchida T, Uematsu H, Nakamura S, Onishi Y, Yamamoto K, Ishii Y: "Phase 1 clinical study of ィイD1123ィエD1I-IBF, a new radioligand for evaluating dopamine DィイD22ィエD2 receptor with SPECT (II); pharmacokinetics study and quantification in the brain."Kakuigaku (Jpn. J. Nucl. Med.). 36(2). 155-168 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Matsumoto H, Tanaka A, Suzuki N, Kondo S, Kato-Azuma M, Yonekura Y: "Metabolism of ィイD1123ィエD1I-IBF in humans."Kakuigaku (Jpn. J. Nucl. Med.). 36(2). 169-177 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Murata T, Omata N, Fujibayashi Y, Waki A, Sadato N, Yoshimoto M, Omori M, Isaki K, Yonekura Y: "Dynamic changes in glucose metabolism induced by thiamine deficiency and its replenishment as revealed by a positron autoradiography technique using rat living brain slices."J. Neurol. Sci.. 164(1). 29-36 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Murata T, Omata N, Fujibayashi Y, Waki A, Sadato N, Yoshida S, Yano R, Yoshimoto M, Isaki K, Yonekura Y: "Dynamic changes in glucose metabolism of living rat brain slices induced by hypoxia and neurotoxic chemical-loading revealed by a positron autoradiography."J. Neural Transm.. 106(11-12). 1075-1087 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Omata N, Murata T, Fujibayashi Y, Waki A, Sadato N, Yoshimoto M, Wada Y, Yonekura Y: "Hypoxic but not ischemic neurotoxicity of free radicals revealed by dynamic changes in glucose metabolsim of fresh rat brain slices on positron autoradiography."J. Cereb. Blood Flow Metab.. 20(2). 350-358 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] 米倉 義晴: "ドパミンD2受容体イメージング剤^<123>I-IBFの第1相臨床試験(第1報)-体内薬物動態及び吸収線量の検討-"核医学. 36巻・2号. 145-153 (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] 米倉 義晴: "ドパミンD2受容体イメージング剤^<123>I-IBFの第1相臨床試験(第2報)-脳内薬物動態及び定量法の検討-"核医学. 36巻・2号. 155-168 (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] 松本博樹: "^<123>I-IBFのヒトにおける代謝に関する検討"核医学. 36巻・2号. 169-177 (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] 鳥塚莞爾: "ドパミンD2受容体イメージング剤^<123>I-IBFの第2相臨床試験-パーキンソン病およびパーキンソン症候群における安全性および有用性の-"核医学. 36巻・8号. 845-863 (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] Tetuhito Murata: "Dynamic changes in glucose metabolism induced by thiamine deficiency and its replenishment as revealed by a positron autoradiography technique using rat living brain slices."J. Neurol. Sci.. 106巻・1号. 29-36 (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] Tetsuhito Murata: "Dynamic changes in glucose metabolism of living rat brain slices induced by hypoxia and neurotoxic chemical-loading revealed by a positron autoradiography."J. Neural Transm.. 106巻・11-12号. 1075-1087 (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] Naoto Omata: "Hypoxic but not ischemic neurotoxicity due to free radicals as revealed by dynamic changes in glucose metabolism of living rat brain slices with a positron autoradiography technique."J. Cereb. Blood Flow metab.. 20巻・2号. 1075-1087 (2000)

    • Related Report
      1999 Annual Research Report
  • [Publications] Tetsuhito Murata: "Dynamic changes in glucose metabolism by lactate loading as revealed by a positron autoradiographictechnique using rat brain slices." NeuroscienceLetters. 249巻2-3号. 155-158 (1998)

    • Related Report
      1998 Annual Research Report
  • [Publications] Tetsuhito Murata: "Triazolam-inducedmodulation of muscarinic acetylcholine receptor in living brain slices as revealedby a new positron-based imaging technique." Journal of Neural Transmission. 105巻10-12号. 1117-1127 (1998)

    • Related Report
      1998 Annual Research Report
  • [Publications] Tetsuhito Murata: "Dynamic changes in glucose metabolism in glucose metabolism induced by thiamine defficiency and its replenishment as revealed by a positronautoradiographic technique using rat brain slices." Journal of Neurological Sciences. 印刷中. (1999)

    • Related Report
      1998 Annual Research Report
  • [Publications] 米倉義晴: "ドパミンD_2受容体イメージング剤^<123>I-IBFの第1相臨床試験(第1報)-体内薬物動態及び吸収線量の検討" 核医学. 36巻2号 印刷中. (1999)

    • Related Report
      1998 Annual Research Report
  • [Publications] 米倉義晴: "ドパミンD_2受容体イメージング剤^<123>I-IBFの第1相臨床試験(第2報)-脳内薬物動態及びその定量法の検討" 核医学. 36巻2号 印刷中. (1999)

    • Related Report
      1998 Annual Research Report
  • [Publications] 松本博樹: "^<123>I-IBFのヒトにおける代謝に関する検討." 核医学. 36巻2号 印刷中. (1999)

    • Related Report
      1998 Annual Research Report
  • [Publications] Shigeru Yoshida: "The effect of neuronal perturbation on the uptake of [^<18>F] 2-fluoro-2-deoxy-D-glucose in brain slices of the rat." Neuroscience Research. (印刷予定). (1998)

    • Related Report
      1997 Annual Research Report

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Published: 1997-04-01   Modified: 2016-04-21  

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