Hepatic targeting of macromolecular MRI contrast agents

Water‐soluble polyester ligands were synthesized by the polycondensation of diethylenetriaminepentaacetic dianhydride (DTPAA) with protected polyalcohol 3‐ O ‐benzyl‐glycerol (3‐ O ‐Bz‐GLYC), pentaerythritol monobenzaldehyde ( S ‐Bz‐PETO) and N ‐benzyldiethanolamine ( N ‐Bz‐DEA), respectively, and the protecting groups were then removed by hydrogenation to give polyesters P(DTPA–GLYC), P(DTPA–PETO) and P(DTPA–DEA). In the same manner, by adding ethylene glycol (EG) monomer into the polymerization system, polyesters P(DTPA–GLYC–EG), P(DTPA–PETO–EG) and P(DTPA–DEA–EG) were also synthesized. Pyridoxamine was chosen as a liver‐targeting group and it was first chlorocarbonylated and then incorporated into polyesters. The polyester ligands containing pyridoxamine group thus prepared were further reacted with GdCl 3 in water at room temperature to give the corresponding hepatic‐targeting polyester gadolinium complexes. These macromolecular ligands and their gadolinium complexes were characterized by 1 H NMR, IR, UV and elementary analysis. Relaxivity studies showed that these polyester gadolinium complexes possess higher relaxation effectiveness than that of the clinically used small molecular gadolinium complex Gd‐DTPA. In vitro cytotoxicity assay demonstrated that these macromolecular ligands and their gadolinium complexes have low cytotoxicity to the human normal liver cells (L‐02). Magnetic resonance imaging of the liver in rats indicated that these polyester MRI contrast agents containing pyridoxamine group exhibit liver‐targeting property. © 2002 Society of Chemical Industry