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

Area of Science:

• Biomaterials Science
• Nanotechnology
• Medical Imaging

Background:

• Current gadolinium (Gd)-based and manganese (Mn)-based small molecular MRI contrast agents have limitations for long-term monitoring and pose safety risks with high or repeated doses.
• There is a need for novel MRI contrast agents with improved safety profiles and efficacy for extended diagnostic applications.

Purpose of the Study:

• To design and synthesize a biocompatible macromolecular MRI contrast agent based on O-carboxymethyl chitosan (CMCS).
• To evaluate the relaxivity, biocompatibility, and in vivo performance of the novel CMCS-(Mn-DTPA)n contrast agent.

Main Methods:

• Synthesis of O-carboxymethyl chitosan-Mn-DTPA (CMCS-(Mn-DTPA)n) macromolecular contrast agent.
• Measurement of relaxivity in aqueous solution compared to Gd-DTPA and Mn-DPDP.
• In vitro assessment of cellular and blood biocompatibility.
• In vivo MRI studies in Sprague Dawley (SD) rats to evaluate signal enhancement, imaging window, and manganese excretion.

Main Results:

• CMCS-(Mn-DTPA)n demonstrated significantly higher relaxivity (3.5x Gd-DTPA, 5.5x Mn-DPDP).
• Enhanced MRI signal intensity in kidney and liver of SD rats at a low dose (0.03 mM Mn/kg b.w.) with a prolonged effective imaging window.
• Good in vitro cellular and blood biocompatibility was observed.
• Manganese was fully excreted from SD rats within 10 days post-administration without inducing liver pathology.

Conclusions:

• CMCS-(Mn-DTPA)n exhibits superior relaxivity, a long effective imaging window, and favorable biocompatibility.
• This novel macromolecular agent represents a promising alternative to current MRI contrast agents, particularly for applications requiring long-term monitoring.
• The findings suggest CMCS-(Mn-DTPA)n has potential as a safe and effective MRI contrast agent.