基于叶酸受体的靶向性钆造影剂的制备及弛豫性能的研究  

Preparation of Targeted Gd^(3+) Contrast Agent Based on Folate-receptor and Its Relaxation

作　　者：周晓力[1] 罗智[1] 唐大宗[2] 夏黎明[2] 孟利平[1] 项光亚[1] 

机构地区：[1]华中科技大学同济医学院药学院,武汉430030 [2]华中科技大学同济医学院附属同济医院放射科,武汉430030

出　　处：《中国药学杂志》2007年第21期1640-1644,共5页Chinese Pharmaceutical Journal

基　　金：国家自然科学基金资助项目(30300430);湖北省自然基金资助项目(2006ABA123)

摘　　要：目的制备基于叶酸受体的靶向大分子磁共振造影剂——叶酸-壳聚糖-(Gd-DTPA)n,并研究其体外弛豫性能。方法在EDC的催化下,将壳聚糖与DTPA反应,制得壳聚糖-DTPA偶联物,然后将该偶联物与叶酸活性酯反应所得产物与GdCl3螯合得到叶酸-壳聚糖-(Gd-DTPA)n。在磁共振仪上测定配合物的体外弛豫时间T1,并分析其弛豫性能R1。结果制得的叶酸-壳聚糖-(Gd-DTPA)n配合物中叶酸的偶联率约为4,Gd-DTPA与壳聚糖的偶联率随着EDC的加入量增大而增大,体外弛豫性能R1约为6.2×10-3L.mmol-1.ms-1,比小分子Gd-DTPA的弛豫性能提高了2.3倍左右。结论成功地制备了叶酸介导的高弛豫效能的靶向性磁共振造影剂。OBJECTIVE To prepare the complexes of folate-chitosan-（ Gd-DTPA ）n a novel kind of folate-receptor-targeted macromolecular MRI contrast agents,and to evaluate their relaxation in vitro. METHODS Catalyzed by EDC at pH 〉 6. 5, chitosan was reacted with DTPA to form chitosan-DTPA, then the complexes of chitosan-chitosan-（ Gd-DTPA ）, were obtained by chelating of GdC13with the product of folate-DTPA coupled with activated folate ester at pH 7 - 8. The in vitro spin-lattice relaxation of these Gd complexes were preliminarily investigated. RESULTS The coupling ratio of folate to chitosan was about 4, and the ratio of Gd-DTPA to chitosan was increased with the increasing of EDC. The relaxation of these complexes was about 6. 2 × 10^-3L · mmol^-1 · ms-1, that＇ s about 2. 3 times as the small molecular Gd-DTPA complex. CONCLUSION The MRI contrast agents mediated by folate had been prepared successfully and had high relaxation.

关 键 词：叶酸 肿瘤靶向 钆造影剂 壳聚糖 体外弛豫性能 

分 类 号：R944[医药卫生—药剂学]