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

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C-11 and I-123 labeled long chain fatty acid derivatives have been reported as useful radiopharmaceuticals 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. After the synthesis, Tc-99m labeling was performed by ligand-exchange reaction with Tc-99m-pertechnetate reduced by Sn(II) glucoheptonate in diluted ethanol solution and purified with HPLC system. Tc-99m labeled long chain fatty acid derivatives were obtained with radiochemical yield of >70 % and radiochemical purity of >95 %.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). Beta oxidation of Tc-99m-MAMA-HDA was investigated using primary cell culture of adult rats myocardium as a preliminary study. The metabolites were analyzed by radio TLC. It was indicated that Tc-99m-MAMA-HDA was metabolized to a short chain fatty acid derivative by the myocardium in vitro.In conclusion, Tc-99m-MAMA-HDA may be recognized as a long chain fatty acid in the myocardium although further examination are required. This Tc-99m labeled compound is useful to evaluate fatty acid metabolism in the myocardium.