Characterization of tumor angiogenesis with dynamic contrast‐enhanced MRI and biodegradable macromolecular contrast agents in mice

Abstract

The efficacy of polydisulfide-based biodegradable macromolecular contrast agents for characterizing tumor angiogenesis was investigated in a mouse model using dynamic contrast-enhanced MRI (DCE-MRI). Biodegradable macromolecular MRI contrast agents, gadopentetate dimeglumine (Gd-DTPA) cystamine copolymers (GDCC), and Gd-DTPA cystine copolymers (GDCP), with molecular weights of 20 and 70 kDa were used in the study. Gadodiamide (Gd [DTPA-BMA]) and albumin labeled with Gd-DTPA [albumin-(Gd-DTPA)] were used as the controls. The DCE-MRI studies were performed in nude mice bearing prostate tumor xenografts from the MDA-PCa-2b cell line. Tumor angiogenic kinetic parameters, including endothelial transfer coefficient (K(PS)), fractional tumor plasma volume (f(PV)), and permeability surface area product (PS), were estimated from the DCE-MRI data using a two-compartment model. The K(PS) and f(PV) values estimated by the biodegradable macromolecular contrast agents were between those estimated by Gd(DTPA-BMA) and albumin-(Gd-DTPA). The parameters estimated by the agent with a slow degradation rate and high molecular weight, GDCP-70 (K(PS) = 2.09 +/- 0.50 ml/min/100 cc and f(PV) = 0.075 +/- 0.021), were closer to those by albumin-(Gd-DTPA) (K(PS) = 1.43 +/- 0.64 ml/min/100 cc and f(PV) = 0.044 +/- 0.007) than by other agents with relatively low molecular weight or rapid degradation rate. The polydisulfide-based biodegradable macromolecular contrast agents are promising for characterizing tumor vascularity and angiogenesis with DCE-MRI.