氨基酸共聚物修饰的生物相容性MRI造影剂

摘要

A macromolecular gadolinium complex was prepared as a magnetic resonance imaging (MRI) contrast agent. An ethlendiamine-modified aspartic acid-valine copolymer was synthesized, conjugated with DOTA, and then chelated with Gd3+ (AI-EDA-DOTA-Gd).T1-relaxivity of the agent (i.e., 12.6 mmol–1×L×s–1) was 2.2 times that of Gd-DOTA (i.e., 5.8 mmol–1×L×s–1). Hemolytic tests showed that the macromolecular contrast agent had good blood compatibility. Histological results demonstrated low toxicity of the agentin vivo. MRI experiments on rats demonstrated a prominent enhancement in liver after AI-EDA-DOTA-Gd injection, which persisted longer than that obtained by Gd-DOTA injection. The mean percentage enhancement in liver parenchyma was (55.1±5.7)% at 30~70 min after injection.%通过天门冬氨酸（Asp）、异亮氨酸（Ile）热缩聚反应，制备了天门冬氨酸-异亮氨酸共聚物（AI），通过乙二胺（EDA）胺化，并与1,4,7,10-四氮杂环十二烷-1,4,7,10-四羧酸（DOTA）连接，再与钆离子（Gd3+）络合，合成了生物相容性大分子磁共振成像（MRI）造影剂——AI-EDA-DOTA-Gd．运用红外光谱（IR）、核磁共振（NMR）、电感耦合等离子谱（ICP）等方法对其进行结构表征，并通过弛豫性能、溶血性质、急性毒性及动物体内成像对其进行综合评价．体外弛豫结果表明，AI-EDA-DOTA-Gd的纵向弛豫效率（r1=12.6 mmol–1×L×s–1）是商用造影剂Gd-DOTA（r1=5.8 mmol–1×L×s–1）的2.2倍．动物组织生理切片和溶血性实验结果说明其具有良好的生物相容性和较低的毒性．动物体内成像结果显示， AI-EDA-DOTA-Gd的最佳成像时间为30~70 min，注射AI-EDA-DOTA-Gd后的肝脏组织信号相比于未注射造影剂时增强了约（55.1±5.7）%．