Tumor Characterization with Dynamic Contrast Enhanced Magnetic Resonance Imaging and Biodegradable Macromolecular Contrast Agents in Mice

To investigate the efficacy of polydisulfide-based biodegradable macromolecular contrast agents of different degradability and molecular weight for tumor characterization based on angiogenesis using dynamic contrast enhanced MRI (DCE-MRI). Biodegradable macromolecular MRI contrast agents, Gd-DTPA cystamine copolymers (GDCC) and Gd-DTPA cystine copolymers (GDCP), with molecular weight of 20 and 70 KDa were evaluated for tumor characterization. Gd(DTPA-BMA) and a prototype of macromolecular contrast agent, albumin-(Gd-DTPA), were used as controls. The DCE-MRI studies were performed in nude mice bearing MDA PCa 2b and PC-3 human prostate tumor xenografts. Tumor angiogenic kinetic parameters including endothelium transfer coefficient (K-trans) and fractional tumor plasma volume (f(PV)) were calculated from the DCE-MRI data using a two-compartment model and compared between the two different tumor models for each contrast agent. There was no significant difference in the f(PV) values between two tumor models estimated with the same agent except for GDCC-70. The K-trans values in both tumor models decreased with the increase of molecular weight of contrast agents. With the same high molecular weight (70 KDa), GDCC-70 showed a higher K-trans values than GDCP-70 due to high degradability of the former in both tumor models (p < 0.05). The K-trans values of MDA PCa 2b tumors were significantly higher than those of PC-3 tumors estimated by Gd(DTPA-BMA), GDCC-20, GDCC-70, GDCP-70, and albumin-(Gd-DTPA) (p < 0.05). The polydisulfide-based biodegradable macromolecular MRI contrast agents are promising in tumor characterization and differentiation with dynamic contrast enhanced MRI.