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Joint Study on Brain Imagimg with Radiolabeled Fatty Acids

Research Project

Project/Area Number 05044152
Research Category

Grant-in-Aid for international Scientific Research

Allocation TypeSingle-year Grants
SectionJoint Research
Research InstitutionTokyo Medical & Dental University

Principal Investigator

HIRAKAWA Kimiyoshi  Tokyo Medical & Dental University, Professor, 医学部, 教授 (00010166)

Co-Investigator(Kenkyū-buntansha) RAPOPORT Sta  米国国立衛生研究所, 神経科学部門, 主任
NARIAI Tadashi  Tokyo Medical & Dental University, Research Associate, 医学部, 助手 (00228090)
RAPOPORT Stanley i.  Laboratory of neurosciences, NIA,NIH,USA,Chief
STANLEY I. R  米国国立衛生研究所, 神経科学部門, 主任
Project Period (FY) 1993 – 1994
Project Status Completed (Fiscal Year 1994)
Budget Amount *help
¥5,000,000 (Direct Cost: ¥5,000,000)
Fiscal Year 1994: ¥2,500,000 (Direct Cost: ¥2,500,000)
Fiscal Year 1993: ¥2,500,000 (Direct Cost: ¥2,500,000)
Keywordsfatty acids / phospholipid / PET / positron emission tomography / palmitate / arachidonate / docosahexaenoate / autoradiography / 燐脂質 / 脳代謝 / サイクロトロン / ホスホリパーゼ
Research Abstract

The aim of our joint project is to develop several positron labeled fatty acid applicable for human brain imaging with positron emission tomography (PET). We have already synthesized C11 labeled palmitate, arachidonate and docosahexaenoate and have been evaluating their incorporation into normal or pathologic brain using large or small animals. Besides the investigator and co-investigators included in this grant, two NIH visiting fellow from Tokyo Medical and Dental University (Drs.Wakabayashi and Arai) were involved in this project.
The following results were obtained. 1) Monkey PET study using C11 labeled fatty acids revealed that the structure and function of brain can be imaged with PET.2) It also was found that C11 labeled saturated palmitate is highly oxidized after intravenous injection. Therefore, an inhibitor of ァーoxidation (methyl palmoxirate) should be applied with to image brain lipid metabolism. 3) Although we have submitted human PET protocol, in which normal volunteers and patients with glioma, Alzheimer disease and Nieman-Pick disease type C will be examined with PET,we could not start human study in this study period because the FDA approval of methyl palmoxirate, which will be expected soon, have not been obtained in study period. 4) In vivo autoradiographic research using rats were conducted in several disease model with reference to glucose metabolism and blood flow study. The study with rats' enucleation model and kindling model have been completed successfully. The pathological changes which could not be detected by glucose metabolism were detected with fatty acid autoradiogram. The study with rats' brain injury model and acute brain ischemia have been started. Preliminary results suggest that the hyper activation of phospholipase A2 can be imaged with radiolabeled unsaturated fatty acid.
Summarizing these results, application of this method in human brain disease will be started in coming year.

Report

(2 results)
  • 1994 Final Research Report Summary
  • 1993 Annual Research Report
  • Research Products

    (24 results)

All Other

All Publications (24 results)

  • [Publications] Nariai T,Suzuki R,Hirakawa K,Maehara T,Ishii K,Senda M: "Vascular Reserve in Chronic Cerebral Ischemia Measured with Acetazolamide Challenge Test:Comparison with Positron Emission Tomography" AJNR Am J Neuroradiol. 16. in press (1995)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1994 Final Research Report Summary
  • [Publications] Nariai T,DeGeorge JJ,Greig NH,Genka S,Rapoport SI,Purdon D: "Difference in rates of incorporation of intravenously injected radiolabeled fatty acids into phospholipids on intravenously implanted tumor and brain in awake rats." Clin Exp Metastasis. 12. 213-225 (1994)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1994 Final Research Report Summary
  • [Publications] Nariai T,Suzuki R,Matsushima Y,Ichimura K,Hirakawa K,Ishii K,Senda M: "Surgically induced angiogenesis to compensate for hemodynamic cerebral ischemia" Stroke. 25. 1014-1021 (1994)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1994 Final Research Report Summary
  • [Publications] Nariai T,DeGeorge JJ,Yamazaki S,Bell J,Hirakawa K,Rapoport SI: "Region specific brain incorporation of intravenously administered radiolabbeled fatty acids into rats'brainexamined with cholionergic stimulation in vivo." Brain Res. (in prep).

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1994 Final Research Report Summary
  • [Publications] Wakabayashi S,Freed LM,Bell JM,Rapoport SI: "In vivo cerebral incorporation of radiolabeled fatty acids after acute unilateral orbital enucleation in adults hooded Long-Evans rats." J Cereb Blood Flow Metab. 14. 312-323 (1994)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1994 Final Research Report Summary
  • [Publications] Wakabayashi et al.: "In vivo imaging of brain incorporation of fatty acids and of 2-deoxyglucose suggests distinct remodeling and functional neuroplastic effects of chronic unilateral visual deprivation in rats." Brain Res. (in press).

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1994 Final Research Report Summary
  • [Publications] ChangMCJ,Wakabayashi S et al.: "The effect of methyl palmoxirate on incorporation of 〔U-14C〕palmitate into rat brain." Neurochem Res. 19. 1217-1223 (1994)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1994 Final Research Report Summary
  • [Publications] Freed LM,Wakabayashi S,Bell JM,Rapoport SI: "Effect of inhibition of β-oxidation on incorporation of 〔U-14C〕palmitate and 〔1-14C〕arachidonate into brain lipids." Brain Res. 645. 41-48 (1994)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1994 Final Research Report Summary
  • [Publications] Arai T,Wakabayashi S,Channing MA,Dunn BB,Der MG,Bell JM,Herscovitch P,Eckelman WC,Rapoport SI,Chang MCJ: "Effect of methyl palmoxirate(MEP) on incorporation of palmitate into monkey brain with PET." J Nucl Med. (in press).

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1994 Final Research Report Summary
  • [Publications] Chang MCJ,Arai T,Freed LM,Wakabayashi S,Channing MA,Dunn BB,Der MG,Bell JM,Herscovitch P,Eckelman WC,Rapoport SI: "Brain incorporation of 〔1-11C〕arachidonate in normocapnic and hypercapnic monkeys:aPET study." J Cereb Blood Flow Metab. (submitted).

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1994 Final Research Report Summary
  • [Publications] Nariai T,Suzuki R,Hirakawa K,Maehara T,Ishii K,Senda M: "Vascular Reserve in Chronic Cerebral Ischemia Measured with Acetazolamide Challenge Test : Comparison with Positron Emission Tomography" AJNR Am J Neuroradiol. 16 (in press). (1995)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1994 Final Research Report Summary
  • [Publications] Nariai T,DeGeorge JJ,Greig NH,Genka S,Rapoport SI,Purdon D: "Difference in rates of incorporation of intravenously injected radiolabeled fatty acids into phospholipids on intravenously implanted tumor and brain in awake rats." Clin Exp Metastasis. 12. 213-225 (1994)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1994 Final Research Report Summary
  • [Publications] Nariai T,Suzuki R,Matsushima Y,Ichimura K,Hirakawa K,Ishii K,Senda M: "Surgically induced angiogenesis to compensate for hemodynamic cerebral ischemia" Stroke. 25. 1014-1021 (1994)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1994 Final Research Report Summary
  • [Publications] Nariai T,DeGeorge JJ,Yamazaki S,Bell J,Hirakawa K,Rapoport SI: "Region specific brain incorporation of intravenously administered radiolabbeled fatty acids into rats' brain examined with cholionergic stimulation in vivo." Brain Res. (in prep).

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1994 Final Research Report Summary
  • [Publications] Wakabayashi S,Freed LM,Bell JM,Rapoport SI: "In vivo cerebral incorporation of radiolabeled fatty acids after acute unilateral orbital enucleation in adults hooded Long-Evans rats." J Cereb Blood Flow Metab. 14. 312-323 (1994)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1994 Final Research Report Summary
  • [Publications] Wakabayashi et al.: "In vivo imaging of brain incorporation of fatty acids and of 2-deoxyglucose suggests distint remodeling and functional neuroplastic effects of chronic unilateral visual deprivation in rats." Brain Res. (in press).

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1994 Final Research Report Summary
  • [Publications] ChangMCJ,Wakabayashi S et al.: "The effect of methyl palmoxirate on incorporation of [U-14C] palmitate into rat brain." Neurochem Res. 19. 1217-1223 (1994)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1994 Final Research Report Summary
  • [Publications] Freed LM,Wakabayashi S,Bell JM,Rapoport SI: "Effect of inhibition of beta-oxidation on incorporation of [U-14C] palmitate and [1-14C] arachidonate into brain lipids." Brain Res. 645. 41-48 (1994)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1994 Final Research Report Summary
  • [Publications] Arai T,Wakabayashi S,Channing MA,Dunn BB,Der MG,Bell JM,Herscovitch P,Eckelman WC,Rapoport SI,Chang MCJ: "Effect of methyl palmoxirate (MEP) on incorporation of palmitate into monkey brain with PET." J Nucl Med. (in press).

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1994 Final Research Report Summary
  • [Publications] Chang MCJ,Arai T,Freed LM,Wakabayashi S,Channing MA,Dunn BB,Der MG,Bell JM,Herscovitch P,Eckelman WC,Rapoport SI: "Brain incorporation of [1-11C] arachidonate in normocapnic and hypercapnic monkeys : a PET study." J Cereb Blood Flow Metab. (submitted).

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1994 Final Research Report Summary
  • [Publications] Nariai T et al.: "Intravenously injected radiolabelled fatty acids image brain tumour phospholipids in vivo:differential uptakes of palmitate,arachidonate and docosahexaenoate" Clin Exp Metastasis. 11. 141-149 (1993)

    • Related Report
      1993 Annual Research Report
  • [Publications] Nariai T et al.: "Difference in rates of incorporation of intravenously injected radiolabeled fatty acids into phospholipids on intravenously implanted tumor and brain in awake rats." Clin Exp Metastasis. 12 (in press). (1994)

    • Related Report
      1993 Annual Research Report
  • [Publications] Yamazaki S et al.: "Effects of pentobarbital on incorporation of plasma palmitate into rat brain" Anesthesiology. 80. 151-158 (1994)

    • Related Report
      1993 Annual Research Report
  • [Publications] Wakabayashi S et al.: "In vivo cerebral incorporation of radiolabeled fatty acids after acute unilateral orbital enucleations in adult hooded Long-Evans rats." J Cereb Blood Flow Metab. 14 (in press). (1994)

    • Related Report
      1993 Annual Research Report

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Published: 1993-04-01   Modified: 2016-04-21  

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