一种新型的以天门冬氨酸-苯丙氨酸共聚物为载体的大分子生物相容性材料(AP-EdA-dOTA-gd)被制备出来作为磁共振成像造影剂.首先合成了天门冬氨酸-苯丙氨酸共聚物,之后利用乙二胺将1,4,7,10-四氮杂环十二烷-1,4,7,10-四乙酸(dOTA)连接到共聚物上,最后将钆离子通过配位的作用方式连接到dOTA上,最终得到大分子AP-EdA-dOTA-gd.体外溶血性试验表明AP-EdA-dOTA-gd具有较好的血液相容性.在P H=5.5的组织蛋白酶b的磷酸缓冲液中,AP-EdA-dOTA-gd能够降解.APEdA-dOTA-gd的体外弛豫效率(15.95 MMOl–1·l·S–1)为目前临床应用的gd-dOTA(5.59MMOl–1·l·S–1)的2.9倍.大鼠肝脏成像实验结果表明,AP-EdA-dOTA-gd对于肝组织的成像增强对比度为63.5±6.1%远高于gd-dOTA(24.2±2.9%).A new biocompatible gadolinium(III)-macromolecule(AP-EDA-DOTA-Gd) was developed as a magnetic resonance imaging(MRI) contrast agent.Poly(aspartic acid-cophenylalanine) was synthesized, modified via ethylenediamine, conjugated with 1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid(DOTA) and finally chelated gadolinium(III), yielding gadolinium(III)-based macromolecule(AP-EDA-DOTA-Gd).The hemolytic tests showed the hemocompatibility of this gadolinium(III)-based macromolecular conjugate.In vitro, AP-EDA-DOTA-Gd could be degraded, when it was incubated with cathepsin B in phosphate buffered solution(p H = 5.5).The T1-relaxivity(15.95 mmol–1·L·s–1) of AP-EDA-DOTA-Gd was 2.9 times of that(5.59 mmol–1·L·s–1) of the clinical MRI contrast agent(Gd-DOTA) at 1.5 T and 25 ℃.The liver enhancement of AP-EDA-DOTA-Gd was 63.5±6.1% during the maximum enhancement time(50-80 min), which was much better than that of Gd-DOTA(24.2±2.9%, 10-30 min).AP-EDA-DOTA-Gd was expected to be a potential liver MRI contrast agent.TheNationalNaturalScienceFoundationofChina(20975097and21305134
