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.

A new type of macromolecular conjugate PL-A2-DOTA-Gd with high T1-relaxivity was synthesized and characterized. The contrast experiments of T1-weighted images of rat liver before and at 60 min after intravenous injection of PL-A2-DOTA-Gd and Gd-DOTA show that the PL-A2-DOTA-Gd has good biocompatibility and hemocompatibility, and can remarkably enhance the signal intensities from the livers of healthy mice injected with lower dosage of PL-A2-DOTA-Gd for a longer period.Figure optionsDownload as PowerPoint slide