Evaluation Of The Biocompatibility Of Macromolecular MRI Contrast Agents Based On O-carboxymethyl Chitosan Derivatives

This paper researched the biocompatibility of three novel macromolecular magnetic resonance imaging (MRI) contrast agents based on O-carboxymethyl chitosan: CMCS-(Gd-DTPA)n, CMCS-(Mn-DTPA)n and CMCS-Ga-(Gd-DTPA)n. CMCS-Ga-(Gd-DTPA)n was liver-specific.The cytotoxicity experiments showed that all three contrast agents possessed few toxicity on HUVEC cells at0.01mM～0.5mM for the concentration of Gd or Mn compared to commercial MRI contrast agents Gd-DTPA. Meanwhile, the hemolysis test results demonstrated that the complexes possessed good blood compatibility, because there was no hemolytic phenomena. The in vitro water proton relaxivity R1of CMCS-(Gd-DTPA)n, CMCS-(Mn-DTPA)n and CMCS-Ga-(Gd-DTPA)n were higher than that of Gd-DTPA. The in vivo MRI experiments revealed a higher signal enhancement and longer retention time of CMCS-(Gd-DTPA)n, CMCS-(Mn-DTPA)n and CMCS-Ga-(Gd-DTPA)n in rats’liver than Gd-DTPA. The results from biodistribution experiments reflected that the content of Gd was little in organs and Gd accumulated more in liver and spleen compared to other organs ten days after intravenous administration. CMCS-Ga-(Gd-DTPA)n displayed more Gd content in liver than CMCS-(Gd-DTPA)n, which confirmed that CMCS-Ga-(Gd-DTPA)n was liver-targeted. Regarding to CMCS-(Mn-DTPA)n、there was little accumulation of Mn in organs.The histological analysis further exploited that CMCS-(Mn-DTPA)n and CMCS-Ga-(Gd-DTPA)n produced no visible damage to the liver, while CMCS-(Gd-DTPA)n induced certain damage in liver.Briefly, the series of experiments above demonstrated that three novel macromolecular MRI contrast agents possessed higher longitudinal relaxivities (R1), excellent signal enhancement in liver and longer retention time in tissues compared to Gd-DTPA. Moreover, they showed low cytotoxicity, hemolysis ratio and little residues of metal ions, which indicated their potential application in clinical diagnose. CMCS-(Gd-DTPA)n showed certain damage to liver, thus whether it’s safe or not needs further investigation. However, CMCS-(Mn-DTPA)n and CMCS-Ga-(Gd-DTPA)n undoubtedly have potential application in future.