A novel manganese chelated macromolecular MRI contrast agent based on O-carboxymethyl chitosan derivatives

[Display omitted] •A macromolecular MRI contrast agent based on chitosan derivatives was synthesized.•It has significant increase in image intensity and longer signal enhancement window.•It displays good biocompatibility in vivo and in vitro at usage dose.•It can be excreted naturally within 10 days from experimental animal body. Currently used Gd-based and Mn-based small molecular MRI contrast agents fail to meet the requirements for the long-term monitoring, and the potential safety risk under high administration dose or repeat dosing needs to be considered. In the present study, a biocompatible macromolecular magnetic resonance imaging (MRI) contrast agents based on O-carboxymethyl chitosan (CMCS), CMCS-(Mn-DTPA)n was designed and synthesized. The relaxivity of CMCS-(Mn-DTPA)n is approximately 3.5 and 5.5 times higher than that of Gd-DTPA and Mn-DPDP in aqueous solution, respectively. The MRI signal intensity in the kidney and liver of Sprague Dawley (SD) rats is significantly increased at a dose of 0.03 mM Mn/kg b.w. CMCS-(Mn-DTPA)n accompanied by a long effective imaging window. According to in vitro studies, CMCS-(Mn-DTPA)n exhibits good cellular and blood biocompatibility at the dose necessary for MRI imaging. Based on the results from in vivo studies, manganese (Mn) is completely excreted from SD rats within ten days after administration and does not exert a pathological effect on the liver. CMCS-(Mn-DTPA)n represents a potentially novel MRI contrast agent due to its excellent relaxivity, long effective imaging window and good biocompatibility.