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Development of Tc-99m labeled long chain fatty acid derivative for myocardial imaging.

Research Project

Project/Area Number 14570853
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field Radiation science
Research InstitutionHAMAMATSU UNIVERSITY SCHOOL OF MEDICINE

Principal Investigator

MAGATA Yasuhiro  Hamamatsu University, School of Medicine Photon Medical Research Center, Professor, 光量子医学研究センター, 教授 (20209399)

Co-Investigator(Kenkyū-buntansha) SAKAHARA Harumi  Hamamatsu University, School of Medicine Faculty of Medicine, Professor, 医学部, 教授 (10187031)
TADAMURA Eiji  Kyoto University, Faculty of Medicine, Assistant Professor, 医学研究科, 助手 (70303831)
Project Period (FY) 2002 – 2003
Project Status Completed (Fiscal Year 2003)
Budget Amount *help
¥3,500,000 (Direct Cost: ¥3,500,000)
Fiscal Year 2003: ¥1,400,000 (Direct Cost: ¥1,400,000)
Fiscal Year 2002: ¥2,100,000 (Direct Cost: ¥2,100,000)
KeywordsBranched Fatty Acid / Tc-99m / SPECT / Rat / Diagnosis / Radiopharmaceutical / Myocardial Function
Research Abstract

C-11 and I-123 labeled long chain fatty acid derivatives have been reported as useful radiopharjnaceuticals for estimation of myocardial fatty acid metabolism. We have reported that ^<99m>Tc-MAMA-HA, middle chain fatty acid derivative, is metabolized by beta-oxidation in a liver and MAMA ligand is useful to attach to the omega-position of fatty acid derivative as a chelating group with Tc-99m. Based on these findings, we focused on developing Tc-99m labeled long chain fatty acid derivative that reflected fatty acid metabolism in the myocardium. We synthesized some long chain fatty acids (carbon length ; 11 (MAMA-DA), 15 (MAMA-HDA)) containing MAMA group in its molecule as a chelating group with Tc-99m. Then, Tc-99m labeling and biodistribution studies were performed. A higher initial uptake of Tc-99m-MAMA-HDA was observed in in vivo animal experiments using mice. The value was half of that by I-125-IPPA (p-iodo-phenyl pentadecanoic acid). β-oxydative metabolite, short chain fatty acid … More derivative, Tc-99m-MAMA-BA was found in urine post-injection of Tc-99m-MAMA-HDA in normal rats. These results showed that Tc-99m-MAMA-HDA was recognized as a long chain fatty acid in the body. β-branched long chain fatty acid derivative, such as I-123-BMIPP, is used in clinical nuclear medicine. The radioactivity is accumulated in the heart by so-called metabolic trapping mechanism and this biological character is very useful for routine use. Then, synthesis of Tc-99m-MAMA-β-methyl-FA was carried out and an expected precursor, Trityl-MAMA-β-methyl-HDA was obtained with 14 steps. After Tc-99m labeling of this new compound, apreliminal biodistribution study was performed in normal mice. Although the radioactivity in the heart was not retained, further investigations may be needed. On the other hand, energy metabolism in the heart of Dahl model rats was investigated using an animal PET scanner and FDG. We established the experimental system and found usefulness of nuclear medicine technique in this field. Less

Report

(3 results)
  • 2003 Annual Research Report   Final Research Report Summary
  • 2002 Annual Research Report
  • Research Products

    (19 results)

All Other

All Publications (19 results)

  • [Publications] Magata Y.: "ATc-99m-Labeled Long Chain Fatty Acid Derivative for Myocardial Imaging."Bioconj Chem. (accepted).

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Iida Y.: "Evaluation of 5-[^11C]Methyl-A-85380 as An Imaging Agent for PET Investigations of Brain Nicotinic Acetylcholine Receptors."J Nucl Med. (accepted).

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Handa N: "The effect of nitroglycerin on myocardial blood flow in various segments characterized by rest-redistribution thallium SPECT"J Nucl Med. 44. 745-751 (2003)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Tadamura E: "Quantitative fluorine 18 deoxyglucose uptake by myocardial positron emission tomography in rats"J Nucl Cardiol. 9. 616-621 (2002)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] 間賀田 泰寛: "「基礎編 心臓核医学で用いる放射性薬剤 PET用製剤」心臓核医学の基礎と臨床改訂版?最新の心臓核医学の手法と臨床応用への手がかり? 玉木長良 編"メジカルセンス. 2 (2003)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Magata Y.: "A Tc-99m-Labeled Long Chain Fatly Acid Derivative for Myocardial Imaging."Bioconj Chem. (accepted).

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Iida Y.: "Evaluation of 5-[^<11>C]Methyl-A-85380 as An Imaging Agent for PET Investigations of Brain Nicotinic Acetylcholine Receptors."J Nucl Med. (accepted).

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Tadamura E.: "The effect of nitroglycerin on myocardial blood flow in various segments characterized by rest-redistribution thallium SPECT"J Nucl Med. 44(4). 745-751 (2003)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Handa N.: "Quantitative fluorine 18 deoxyglucose uptake by myocardial positron emission tomography in rats."J Nucl Cardiol. 9(6). 616-621 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Magata Y.: "Development of Injectable O-15 Oxygen and Estimation of Rat OEF."J Cereb Blood Flow Metabol. 23・6. 371-373 (2003)

    • Related Report
      2003 Annual Research Report
  • [Publications] Ishida Y.: "Changes in dopamine D_2 receptors and 6-[^<18>F]fluoro-L-3,4-dihydroxy-phenylalanine uptake in the brain in 6-hydroxydopamine lesioned rats"Neurodegerative Disease. (accepted).

    • Related Report
      2003 Annual Research Report
  • [Publications] Iida Y.: "Evaluation of 5-[^<11>C]Methyl-A-85380 as An Imaging Agent for PET Investigations of Brain Nicotinic Acetylcholine Receptors."J Nucl Med. (accepted).

    • Related Report
      2003 Annual Research Report
  • [Publications] Magata Y.: "A Tc-99m-Labeled Long Chain Fatty Acid Derivative for Myocardial Imaging."Bioconj Chem. (accepted).

    • Related Report
      2003 Annual Research Report
  • [Publications] 間賀田泰寛: "「基礎編 心臓核医学で用いる放射性薬剤 PET用製剤」心臓核医学の基礎と臨床改訂版 最新の心臓核医学の手法と臨床応用への手がかり 玉木長良 編"メジカルセンス. 2 (2003)

    • Related Report
      2003 Annual Research Report
  • [Publications] H.Kawashima: "Brain extraction of 4-(4-chlorophenyl)-1-[4-(4-fluorophenyl)-4-oxobutyl]pyridinium ion (HPP+),a neurotoxic metaboliteo of haloperidol : sudies using [3H]HPP+"Jpn. J. Pharmacol.. 89・4. 426-428 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] N.Handa: "Quantitative FDG-uptake by myocardial positron emission tomography in rats"J. Nucl. Cardiol.. 9・6. 616-621 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] Y.Magata: "Simple analytical method of [11C]-flumazenil metabolite in blood"J. Nucl Med. 44・3. 417-421 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] Y.Magata: "Development of injectable O-15 oxygen and estimation of rat OEF"J. Cereb. Blood Flow Metabol.. 23(accepted). (2003)

    • Related Report
      2002 Annual Research Report
  • [Publications] 間賀田 泰寛: "特集加速するPET導入と核医学-PET薬剤の現状とその利用-"月刊新医療. 4 (2002)

    • Related Report
      2002 Annual Research Report

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Published: 2002-04-01   Modified: 2016-04-21  

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