Contrast agents special for liver are always required to have a relatively longer metabolic time and a stable contrast effect in liver tissue.Therefore

D-lactobionic acid residues

which are generally used as liver-targeted groups

were introduced here.Single N-hydroxysuccinimide active ester of DTPA (SuO-DTPA-Tyr) was synthesized as the ligand of gadolinium (III) ion

forming the basic structure of non-ionic contrast agent.Three α

β poly(L-aspartic acid) derivatives (PD0

PD1 and PD3) with different D-lactobionic acid residue contents were synthesized by conjugation of D-lactobionic acid and single N-hydroxysuccinimide active ester of DTPA with α

β-poly[(2-aminoethyl) L-aspartamide]

respectively.Polymeric gadolinium (III) complexes (PD0-Gd

PD1-Gd and PD3-Gd) were prepared by the reaction of α

β-poly(L-aspartic acid) derivatives with GdCl3.6H2O.The contents of D-lactobionic residues and gadolinium (III) were determined by quantitative13C-NMR and ICP

respectively.Properties of these polymeric contrast agents were evaluated here.Cytotoxicity test shows that all the polymer ligands (PC0

PC1 and PC3) have better cell viability rate than that of poly(L-lysine) with corresponding concentrations.The value of cell viability rate rises with the increase of D-lactobionic acid residue content.The reason is the D-lactobionic acid residues mostly shield the positive charge of backbone

which blocks the delivery of carrier to the cells.Compared with the commercial contrast agents

polymer complexes have the same level of cytotoxicity.However

their relaxivities (7.77

8.00 and 9.48 mmolL-1s-1 for PD0-Gd

PD1-Gd and PD3-Gd

respectively) are obviously higher than that of commercial contrast agents (5.95 mmolL-1s-1 for dimeglnmine gadopentetate).That is because the mobility of polymer molecules is lower than that of small molecules

which leads to an increase of relaxivities.Experiments in vivo were carried out on ICR mice

which were divded into 3 groups for 3 different contrast agents (PD0-Gd

PD3-Gd and Dimeglnmine Gadopentetate for commercial used).Mice for each contrast agent were also divided into 5 groups (6 mice each) for testing in different time after injections.As the result shows

polymeric complex with liver targeted groups gives a better result than that of complex without liver targeted groups.All of the polymeric complexes give much better image contrast effects and longer circular time than that of commercial contrast agent in mice livers.During the first 6 h after being injected

polymeric complexes with D-lactobionic residues have much lower metabolism rate than those without D-lactobionic residues and gives the clearest liver image among all those contrast agents

even though the signal is not the strongest one which mostly depends on the relaxivities.Besides that

mice liver with liver-targeted complexes show a stable and clear image statistically.After 6 h

metabolism rate of liver targeted polymer complex increases and has almost same metabolism rate as that of commercial contrast agent.Those results illustrate that the introduction of D-lactobionic acid residues can moderately prolong the metabolic time in liver and stabilize the liver signal enhanced by contrast agents.