2003 Fiscal Year Final Research Report Summary
Development of Tc-99m labeled long chain fatty acid derivative for myocardial imaging.
| Project/Area Number |
14570853
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Radiation science
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| Research Institution | HAMAMATSU UNIVERSITY SCHOOL OF MEDICINE |
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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)
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| 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)
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| Project Period (FY) |
2002 – 2003
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| Keywords | Branched Fatty Acid / Tc-99m / SPECT / Rat / Diagnosis / Radiopharmaceutical / Myocardial Function |
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| 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
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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
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