4-甲基咪唑双膦酸的合成及其<sup>99</sup>Tc<sup>m</sup>标记

4-甲基咪唑双膦酸的合成及其⁹⁹Tc^m标记

摘要: 以4-甲基咪唑为原料，通过N-烷基化、酯水解和磷酸酰化三步反应，合成1-羟基-2-（4-甲基-1H-咪唑基）-乙烷-1，1-双膦酸（M₄IDP）,目标产物和重要中间体通过IR、MS及¹H NMR进行结构鉴定;采用Na⁹⁹Tc^mO₄标记M₄IDP，得到标记物⁹⁹Tc^m-M₄IDP，并测定其体外稳定性。结果显示，标记物的最佳标记条件为：反应时间30 min，反应体系pH为6，SnCl₂·2H₂O用量100 μg，配体用量5 mg。在此条件下，标记率>95%，室温下存放6 h，放化纯度＞95%，说明⁹⁹Tc^m-M₄IDP具有较好的体外稳定性。

Abstract: 1-Hydroxy-2-（4-methyl-1H-imidazoleyl）-ethylidene-1,1-bisphosphonic（M₄IDP）was prepared by three steps of N-alkylation、ester hydrolation and phosphoric acid acylation from the raw material 4-methyl-1H- imidazole. The structures of intermediate and target compounds were identified by Elemental Analysis、IR、MS and ¹H NMR. Then M₄IDP was directly labeled by Na⁹⁹Tc^mO₄ to afford ⁹⁹Tc^m-M₄IDP. The results showed that the best labeling conditions were 30 minutes reaction time， pH 6，100 μg SnCl₂·2H₂O， and 5 mg M₄IDP. In this condition, the labeling yield was more than 95% and ⁹⁹Tc^m-M₄IDP showed good biological stability in vitro.