Synthesis And Characterization Of Macromolecular MRI Contrast Agents Based On Water-soluble Chitosan Derivatives

Magnetic resonance imaging (MRI) has emerged as a leading noninvasive diagnostic technique in clinical diagnostics and research, and the contrast agent is an important section of MRI. MRI contrast agents may increase the signal contrast between normal tissues and abnormal ones. In the paper the main contents are synthesis of macromolecular contrast agents and study of the properties.1. DTPA was conjuncted to O-carboxymethyl chitosan (CMCS), getting CMCS-DTPA. D-galactose(Ga) also was conjuncted to CMCS-DTPA and CMCS-Ga-DTPA was obtained. CMCS-DTPA and CMCS-Ga-DTPA chelate with Gd3+and macromolecular contrast agents CMCS-(Gd-DTPA)n and CMCS-Ga-(Gd-DTPA)n were obtained, respectively.2. To improve the relaxivity and consider the tumor-targeting, another tumor-targeted chitosan derivative O-succinyl chitosan(SCCS) was synthesized, and then macromolecular complexes of SCCS with manganese (Ⅱ)-diethylenetriaminepentaaceticacid (SCCS-(Mn--DTPA)n) and gadolinium(Ⅲ)-diethylenetriaminepentaaceticacid (SCCS-(Gd-DTPA)n) were synthesized as potential magnetic resonance imaging(MRI) contrast agents.3. The relaxivities were characterized at Siemens Trio3T MRI Scanner in vitro. It was found that the complexes had a favorable influence on water protons relaxation time, and the relaxivities of CMCS-(Gd-DTPA)n and CMCS-Ga-(Gd-DTPA)n were1.6and2.3times higher than that of Gd-DTPA. The longitudinal relaxivities (R1) of SCCS-(Mn-DTPA)n and SCCS-(Gd-DTPA)n were2.0and3.5times as great as that of clinical contrast agent Gd-DTPA, respectively. The contrast enhanced MR imaging of the agents was evaluated in Sprague-Dawley rats on a Siemens Trio3T MRI Scanner. CMCS-(Gd-DTPA)n and CMCS-Ga-(Gd-DTPA)n show better signal enhancement than Gd-DTPA and the highest signal enhancement was observed after injection1hour and about25%signal enhancement was still remained after injection12h. Both SCCS and CMCS based macromolecular contrast agents showed higher signal enhancement and longer retention time than Gd-DTPA. In vitro biocompatibility experiments demonstrated the macromolecular contrast agents showed little cytotoxicity and good blood compatibility at low concentrations.