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

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.