MRI Contrast Agent Based on Zwitterionic Metal-chelating Polymer for Hepatorenal Angiography and Tumor Imaging
MRI contrast agent can improve the ability of MRI in differentiating diseased and healthy tissues, and has been widely used in clinical diagnosis, such as paramagnetic Gd(III)-chelates. However, the enhancement effect of small molecular MRI contrast agents is unsatisfied due to their relative high rotation rate. Furthermore, the small molecular contrast agents also suffers from the short blood half-life and nonspecific extracellular diffusion in tissues, which also restricts their applications. To address these issues, we developed a macromolecular MRI contrast agent based on zwitterionic mental-chelating polymer. Poly (acrylic acid) (PAA) was chosen as the main chain, and the diethylenetriamine pentaacetic acid (DTPA) molecule as metal-chelating groups was coupled through the carboxyl groups of PAA using diethylenetriamine (DET) as a linker. The macromolecular MRI contrast agent constructed by chelating with Gd3+ (Gd-PAA), exhibited much higher longitudinal relaxation rate (r1) than the clinical contrast agent Gd-DTPA. Importantly, due to the stealth ability of zwitterionic structure, Gd-PAA can reside in the blood long enough without microvascular leakage in extracellular space of normal tissue, which allow it to be used for precise blood MR imaging, such as hepatorenal angiography, but also for tumor imaging because of the enhanced permeability and retention (EPR) effect. Besides, the result of long-term toxicity tests highlights the safety feature of the current contrast agent as well. Hence, the current contrast agent overcomes the defect of traditional small molecular Gd(III)-based T1-weighted contrast agents, and shows great prospects for future clinical applications.