Polyaspartamide gadolinium complexes containing sulfadiazine groups as potential macromolecular MRI contrast agents

Abstract

Both diethylenetriaminepentaacetic acid (DTPA) and sulfadiazine (SD) were incorporated into polyaspartamides with different side chains, including poly-alpha,beta-[N-(2-hydroxyethyl)-L-aspartamide] (PHEA), poly-alpha,beta-[N- (3-hydroxypropyl)-L-aspartamide] (PHPA), poly-alpha,beta-[N-(2-aminoethy1)-L-aspartamide] (PAEA), poly-alpha,beta-[N-(4-aminobuty1)-L-aspartamide] (PABA), and poly-alpha,beta-[N-(6-aminohexyl)-L-aspartamide] (PAHA). The polyaspartamide ligands containing DTPA and SD groups were further reacted with gadolinium chloride to give the corresponding macromolecular gadolinium complexes. Experimental data of 1H NMR, IR, UV, and elemental analysis exhibited the formation of the polyaspartamide ligands and gadolinium complexes. Relaxivity studies indicated that the macromolecular chelates possess higher relaxivities than that of the clinically used Gd-DTPA. MR imaging showed that the macromolecular chelate PAEA-Gd-DTPA-SD greatly enhanced the contrast of MR images of hepatoma in the lower limb of mice and provided prolonged intravascular duration. Thus the polyaspartamide gadolinium complex containing SD groups is expected to be used as the potential macromolecular MRI contrast agents for hepatoma in mice.