叶酸介导的靶向性钆造影剂的制备及弛豫性能研究

Preparation and Relaxivity of Folate-mediated Targeting Gd^(3+) Contrast Agent

在弱碱性的条件下,叶酸活化酯与牛血清白蛋白(BSA)反应生成叶酸-牛血清白蛋白偶联物(叶酸-BSA),该偶联物再与二乙三胺五乙酸(DTPA)的酸酐反应,最后与GdCl_3进行螯合制得叶酸-BSA-(Gd-DTPA)n。配合物的结构通过紫外光谱法进行了鉴定,并定量测定了配合物中叶酸、Gd-DTPA对BSA的偶联率。通过测定配合物的体外弛豫时间T_1,进一步分析其弛豫性能R_1。结果表明本研究制得的叶酸-BSA-(Gd-DTPA)_n配合物中叶酸的偶联率约为5,体外弛豫性能R_1约为6×10-3L·mmol^(-1)·ms^(-1),与未偶联叶酸的BSA-(Gd-DTPA)_n的弛豫性能无显著性差异,且比小分子Gd-DTPA的弛豫性能提高了3倍左右。

Under weak base condition, Bovine serum albumin （BSA） was reacted with the activated folate firstly; then the conjugates were coupled with Diethylene triamine pentaacetic dianhydride （cDTPAA） to form Folate- BSA-DTPA; finally, these coupled compounds were chelated with GdCl3. All complexes were characterized by UV, the ratios of folate and Gd-DTPA to BSA were determined by UV and ICP-AES methods, respectively. The spin-lattice relaxivity of the Gd complexes in vitro was analyzed. As a result, the ratio of folate to BSA was about 5, and the relaxivity was about 6×10^-3 L·mmol^-1·ms^-1 enhanced three times compared to the small molecular GdDTPA, though there was no difference in relaxivity between folate-BSA-（Gd-DTPA）n and BSA-（Gd-DTPA）n.