Arano Y, Magata Y, Horiuchi K, Matsumoto K, Fujibayashi Y, Ohmomo Y, Tanaka C, Saji H, Yokoyama A
Department of Radiopharmaceutical Chemistry, Faculty of Pharmaceutical Sciences, Kyoto University, Japan.
Int J Rad Appl Instrum A. 1989;40(9):745-9. doi: 10.1016/0883-2889(89)90091-9.
For the development of 62Cu labeled fatty acid analogs, two fatty acid analogs, containing dithiosemicarbazone (DTS) molecule as the 62Cu coordinating site, were designed and synthesized: a fatty acid analog containing DTS molecule at the omega-position, (a) the 12,13-dioxotetradecanoic acid di(N-methyl-thiosemicarbazone) (FA-DTS), and an omega-phenyl fatty acid analog containing DTS molecule at the para-position, (b) the p-carboxyundecylphenylglyoxal-di (N-methylthiosemicarbazone] (PFA-DTS). FA-DTS was synthesized by the reaction of ethyl diethoxyacetate with ethyl 11-bromonundecanate by successive decarboxylation and hydrolysis and final condensation with N-methylthiosemicarbazide. PFA-DTS was synthesized by the Friedel-Craft acylation of ethyl 11-phenylundecanate, selenium oxidation of the acetophenone derivative, followed by the condensation with N-methylthiosemicarbazide. Radiolabeling of FA-DTS and PFA-DTS with [64Cu]copper acetate was simple, rapid and quantitative. When injected into mice, both compounds were distributed and retained in the myocardium. These results offer a good basis for further development of 62Cu labeled fatty acid analogs.
为了开发62Cu标记的脂肪酸类似物，设计并合成了两种以二硫代氨基脲（DTS）分子作为62Cu配位位点的脂肪酸类似物：一种在ω位含有DTS分子的脂肪酸类似物，（a）12,13 - 二氧代十四烷酸二（N - 甲基 - 硫代氨基脲）（FA - DTS），以及一种在对位含有DTS分子的ω - 苯基脂肪酸类似物，（b）对 - 羧基十一烷基苯基乙二醛 - 二（N - 甲基硫代氨基脲）（PFA - DTS）。FA - DTS是通过二乙氧基乙酸乙酯与11 - 溴代十一烷酸乙酯反应，经连续脱羧、水解，最后与N - 甲基硫代氨基脲缩合而成。PFA - DTS是通过11 - 苯基十一烷酸乙酯的傅克酰基化反应、苯乙酮衍生物的硒氧化反应，然后与N - 甲基硫代氨基脲缩合而成。用[64Cu]醋酸铜对FA - DTS和PFA - DTS进行放射性标记简单、快速且定量。当注入小鼠体内时，这两种化合物都分布并保留在心肌中。这些结果为进一步开发62Cu标记的脂肪酸类似物提供了良好的基础。
