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

C-11和I-123标记的长链脂肪酸衍生物已被报道为估计心肌脂肪酸代谢的有用放射性药物。我们已经报道了中链脂肪酸衍生物~(99)m和~(99)m-Tc-MAMA-HA在肝脏中通过β-氧化代谢，而MAMA配体与~(99m)Tc作为螯合基团连接在脂肪酸衍生物的欧米位上。基于这些发现，我们致力于开发能够反映心肌脂肪酸代谢的~(99)Tc标记长链脂肪酸衍生物。我们合成了一些分子中含有MAMA基团的长链脂肪酸(碳长：11(MAMA-DA)，15(MAMA-HDA))作为与99m的螯合基团。然后，进行~(99m)Tc标记和生物分布研究。在小鼠的体内动物实验中，观察到较高的初始摄取率。此值是I-125-IPPA(对碘苯基十五烷酸)的一半。β-氧化代谢物，短链脂肪酸…正常大鼠注射99m-MAMA-HDA后，尿液中有较多的衍生物--~(99)m-MAMA-BA。结果表明，~(99m)Tc-MAMA-HDA是体内公认的一种长链脂肪酸。β支链长链脂肪酸衍生物，如I-123-BMIPP，广泛应用于临床核医学。放射性是通过所谓的代谢捕获机制在心脏中积累的，这一生物学特性对日常使用非常有用。然后合成了99m-MAMA-β-甲基-FA，经过14步反应得到了预期的前驱体--三甲基-MAMA-β-甲基-HDA。在~(99m)Tc标记后，进行了正常小鼠的轴周生物分布研究。虽然心脏中的放射性没有被保留，但可能需要进一步的研究。另一方面，使用动物PET扫描仪和FDG研究DAHL模型大鼠心脏的能量代谢。我们建立了实验系统，发现了核医学技术在这一领域的应用。较少

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