Synthesis and Evaluation of a Biocompatible Macromolecular Gadolinium Compound as a Liver-Specific Contrast Agent for MRI

Abstract

A new macromolecular biocompatible gadolinium chelate complex (PAI-N2-DOTA-Gd) as a liver-specific magnetic resonance imaging (MRI) contrast agent was synthesised and evaluated. An aspartic acid–isoleucine copolymer was chemically linked with Gd-DOTA via ethylenediamine to give PAI-N2-DOTA-Gd. In vitro, the T1-relaxivity of PAI-N2-DOTA-Gd (14.38 mmol–1⋅L⋅s–1, 0.5 T) was much higher than that of the clinically used Gd-DOTA (4.96 mmol–1⋅L⋅s–1, 0.5 T), with obvious imaging signal enhancement. In the imaging experiments in vivo, PAI-N2-DOTA-Gd exhibited good liver selectivity, and had a greater intensity enhancement (68.8 ± 5.6 %) and a longer imaging window time (30–70 min), compared to Gd-DOTA (21.1 ± 5.3 %, 10–30 min). Furthermore, the in vivo histological studies of PAI-N2-DOTA-Gd showed a low acute toxicity and desirable biocompatibility. The results of this study indicate that PAI-N2-DOTA-Gd is a feasible liver-specific contrast agent for MRI.