新型生物相容性大分子磁共振成像造影剂的性质研究

将天冬氨酸与亮氨酸反应,合成了天冬氨酸-亮氨酸共聚物(PL),通过乙二胺将钆-1,4,7,10-四氮杂环十二烷-1,4,7,10-四乙酸(Gd-DOTA)连接到PL上,制备了大分子磁共振成像造影剂PL-A2-DOTA-Gd,通过核磁碳谱、凝胶色谱等方法对其结构进行了表征,利用细胞毒性实验、溶血性实验、体外弛豫效率测定以及体内动物磁共振成像等方法对其性能进行了评估。研究表明,PL-A2-DOTA-Gd的细胞毒性远低于临床应用的造影剂Gd-DOTA,且其弛豫效率(15.3 L/(mmol·s))是Gd-DOTA(5.8 L/(mmol·s))的2.6倍。大分子磁共振成像造影剂PL-A2-DOTA-Gd具有良好的血液相容性,对昆明小鼠的肝脏信号的增强效果约为Gd-DOTA的3.1倍,且能在较长时间内保持良好稳定的增强效果。

Preparation of Novel Biocompatible Macromolecular Magnetic Resonance Imaging Contrast Agent

Poly (aspartic acid-co-leucine) (PL) synthesized with aspartic acid and leucine was conjugated to 1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid (DOTA) by ethylenediamine. Then the compound obtained was chelated with gadolinium (III) to form PL-A₂-DOTA-Gd. The structure of PL-A₂-DOTA-Gd was characterized by nuclear magnetic resonance and gel chromatography and its performance was evaluated by cytotoxicity test, heamolysis test, in vitro relaxivity determination and animal in vivo magnetic resonance characterization. PL-A₂-DOTA-Gd exhibited much lower cytotoxicity than Gd-DOTA. The T1-relaxivity of PL-A₂-DOTA-Gd (15.3 mM⁻¹ s⁻¹) was 2.6 times than that of Gd-DOTA (5.8 mM⁻¹ s⁻¹) in D₂O. The results of magnetic resonance imaging (MRI) experiments showed a significant enhancement in the rat liver imaging after the intravenous administration of PL-A₂-DOTA-Gd. In addition, the imaging time persisted by using PL-A₂-DOTA-Gd than that of Gd-DOTA and the imaging effect of liver tissue was enhanced by an average of 65.1% ± 5.2% and 21.3% ± 4.9% for PL-A₂-DOTA-Gd and Gd-DOTA, respectively.