Assessment of tumor angiogenesis: Dynamic contrast-enhanced MRI with paramagnetic nanoparticles compared with Gd-DTPA in a rabbit Vx-2 tumor model

The purpose of this study was to evaluate the suitability of a macromolecular MRI contrast agent (paramagnetic nanoparticles, PNs) for the characterization of tumor angiogenesis. Our aim was to estimate the permeability of PNs in developing tumor vasculature and compare it with that of a low molecular weight contrast agent (Gd-DTPA) using dynamic contrast-enhanced MRI (DCE).Male NewZealand white rabbits (n=5) underwent DCEMRI 12-14 days after Vx-2 tumor fragments were implanted into the left hind limb. Each contrast agent (PNs followed by Gd-DTPA) was evaluated using a DCE protocol and transendothelial transfer coefficient (K_i)maps were calculated using a two-compartmentmodel. Two regions of interest (ROIs) were located within the tumor core and hindlimb muscle and five ROIs were placed within the tumor rim. Comparisons were performed using repeated measures analysis of variance (ANOVA). The K_i values estimated using PNs were significantly lower than those obtained for Gd-DTPA (p=0.018). When PNs and Gd-DTPA data were analyzed separately, significant differences were identified among tumor rim ROIs for PNs (p<0.0001), but not for Gd-DTPA data (p=0.34). The mean K_i for the tumor rim was significantly greater than that of either the core or the hindlimb muscle for both contrast agents (p<0.05 for each comparison). In summary, the extravasation of Gd-DTPA was far greater than that of PNs, suggesting that PNs can reveal regional differences in tumor vascular permeability that are not otherwise apparent with clinical contrast agents such as Gd-DTPA. These results suggest that PNs show potential for the noninvasive delineation of tumor angiogenesis.