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Analysis of brain/heart pathogenesis based on mitochondiral function and its application to nuclear medicine.

Research Project

Project/Area Number 11670882
Research Category

Grant-in-Aid for Scientific Research (C)

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

Principal Investigator

FUJIBAYASHI Yasuhisa  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)

Project Period (FY) 1999 – 2000
Project Status Completed (Fiscal Year 2000)
Budget Amount *help
¥3,000,000 (Direct Cost: ¥3,000,000)
Fiscal Year 2000: ¥1,100,000 (Direct Cost: ¥1,100,000)
Fiscal Year 1999: ¥1,900,000 (Direct Cost: ¥1,900,000)
Keywordselectron transport / hypoxia / ischemia / nuclear medicine / radiopharmaceutical / copper / ミトコンドリア / 脳障害 / エネルギー代謝 / ラット / マウス / 脳組織切片
Research Abstract

Mitochondiria is an important intracellular organism for aerobic energy production, having its own gene and expression system. Normally, mitochondria and other intracellular origanisms are closely linkaged, but failture in this linkage is said to be a cause of oxidative stress such as ischemia-reperfison injury, especially in brain or heart. Understanding the process of failure in this linkage will bring a new sight of pathogenesis of ishcemic disease in brain/heart and allow us to develop new diagnostic method in nuclear medicine. In this research, new radioactive copper labeled radiopharmacetucals, have been developmed and electron transport failure could be visualized in diseased animal models as well as human patients. Radioiodinated Fatty acid derivative has been evaluated as a marker of myocardial energy failure, and its usefulness could be clarified. Dynamic analysis of brain uptake of fluorine-18-labeled fluorodeoxyglucose (FDG) in ischemic/hypoxic brain slices brought us an difference in contribution of radical formation and glutamate release to the reversibility of damage in the brain. This methodology allows us to clarify the drug effect on neuronal damage under strictly controlled conditions.
As an additional research, hypoxia tolerance of tumors can be also studied in comparison with hypoxia of non-tumor tissues. Based on the results of this work, development of therapeutic radiopharmaceutical for hypoxic tumor selective radiotherapy could be performed successfully.

Report

(3 results)
  • 2000 Annual Research Report   Final Research Report Summary
  • 1999 Annual Research Report
  • Research Products

    (24 results)

All Other

All Publications (24 results)

  • [Publications] Fujibayashi,Y.: "Comparative studies of Cu-64-ATSM and C-11-acetate in an acute myocardial infarction model : ex vivo imaging of hypoxia in rats."Nucl Med Biol. 26(1). 117-121 (1999)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Lewis,J.S.: "Evaluation of 64Cu-ATSM in vitro and in vivo in a hypoxic tumor model."J Nucl Med. 40(1). 177-183 (1999)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Takahashi,N.: "Evaluation of 62Cu labeled diacetyl-bis (N4-methylthiosemicarbazone) as a hypoxic tissue tracer in patients with lung cancer."Ann Nucl Med. 14(5). 323-328 (2000)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Horiuchi,K.: "The development of (99m) Tc-analog of Cu-DTS as an agent for imaging hypoxia."Nucl Med Biol. 27(4). 391-399 (2000)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Lewis,J.S.: "Copper-64-diacetyl-bis (N4-methylthiosemicarbazone) : An agent for radiotherapy."Proc Natl Acad Sci. 98(3). 1206-1211 (2001)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Murata,T.: "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(和文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Fujibayashi, Y., et al.: "Comparative studies of Cu-64-ATSM and C-11-acetate in an acute myocardial infarction model : ex vivo imaging of hypoxia in rats."Nucl Med Biol. 26 (1). 117-21 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Lewis, J.S., et al.: "Evaluation of 64Cu-ATSM in vitro and in vivo in a hypoxic tumor model."J Nucl Med. 40 (1). 177-83 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Takahashi, N., et al.: "Evaluation of 62Cu labeled diacetyl-bis (N4-methylthiosemicarbazone) as a hypoxic tissue tracer in patients with lung cancer."Ann Nucl Med. 14 (5). 323-8 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Lewis, J.S., et al.: "Copper-64-diacetyl-bis (N4-methylthiosemicarbazone) : An agent for radiotherapy."Proc Natl Acad Sci. 98 (3). 1206-1211 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Horiuchi, K., et al.: "The development of (99m) Tc-analog of Cu-DTS as an agent for imaging hypoxia."Nucl Med Biol. 27 (4). 391-9 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Murata, T., et al.: "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
      2000 Final Research Report Summary
  • [Publications] Murata, T., et al.: "Dynamic changes in glucose metabolism of living rat brain slices induced by hypoxia and neurotoxic chemical-loading revealed by positron autoradiography."J Neural Transm. 106 (11-12). 1075-87 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Omata, N., et al.: "Hypoxic but not ischemic neurotoxicity of free radicals revealed by dynamic changes in glucose metabolism of fresh rat brain slices on positron autoradiography."J Cereb Blood Flow Metab. 20 (2). 350-8 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Nohara, R., et al.: "Basic kinetics of 15-(p-iodophenyl)-3-R, S-methylpentadecanoic acid (BMIPP) in canine myocardium."Int J Card Imaging. 15 (1). 11-20 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Hosokawa, R., et al.: "Myocardial metabolism of 123I-BMIPP in a canine model with ischemia : implications of perfusion-metabolism mismatch on SPECT images in patients with ischemic heart disease."J Nucl Med. 40 (3). 471-8 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Kataoka, K., et al.: "Myocardial lipid metabolism in compensated and advanced stages of heart failure : evaluation by canine pacing model with BMIPP."J Nucl Med. 42 (1). 124-9 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Fujibayashi,Y.: "Comparative studies of Cu-64-ATSM and C-11-acetate in an acute myocardial infarction model : ex vivo imaging of hypoxia in rats."Nucl Med Biol. 26(1). 117-121 (1999)

    • Related Report
      2000 Annual Research Report
  • [Publications] Lewis,J.S.: "Evaluation of 64Cu-ATSM in vitro and in vivo in a hypoxic tumor model."J Nucl Med. 40(1). 177-183 (1999)

    • Related Report
      2000 Annual Research Report
  • [Publications] Takahashi,N.: "Evaluation of 62Cu labeled diacetyl-bis (N4-methylthiosemicarbazone) as a hypoxic tissue tracer in patients with lung cancer."Ann Nucl Med. 14(5). 323-328 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] Lewis,J.S.: "Copper-64-diacetyl-bis (N4-methylthiosemicarbazone): An agent for radiotherapy."Proc Natl Acad Sci. 98(3). 1206-1211 (2001)

    • Related Report
      2000 Annual Research Report
  • [Publications] Horiuchi,K.: "The development of (99m) Tc-analog of Cu-DTS as an agent for imaging hypoxia."Nucl Med Biol. 27(4). 391-399 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] Murata,T.: "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)

    • Related Report
      2000 Annual Research Report
  • [Publications] Yasuhisa Fujibayashi, et al.: "Neurotoxicity after hypoxia/during ischemia due to glutamate with/without free radicals as revealed by dynamic changes in glucose metabolism."Brain Research. (in press).

    • Related Report
      1999 Annual Research Report

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Published: 1999-04-01   Modified: 2016-04-21  

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