MR imaging characterization of microvessels in experimental breast tumors by using a particulate contrast agent with histopathologic correlation

PURPOSE: To define the diagnostic potential of magnetic resonance (MR) imaging enhanced with ultrasmall superparamagnetic iron oxide (USPIO) particles for the quantitative characterization of tumor microvasculature. MATERIALS AND METHODS: NC100150 injection, a USPIO in clinical trials, and albumin-(Gd-DTPA)(30) were compared at MR imaging on sequential days in the same 19 rats with mammary tumors. Kinetic analysis of dynamic T1-weighted three-dimensional spoiled gradient-recalled imaging data with a two-compartment bidirectional model yielded MR imaging estimates of microvascular permeability (K-PS) and fractional plasma volume (fPV) for each contrast medium. RESULTS: Strongly positive and significant correlations were observed between MR imaging-derived K-PS estimates and histologic tumor grade with either the soluble albumin-(Gd-DTPA)(30) (r = 0.88; P < .001) or larger particulate USPIO (r = 0.82; P < .001). A significant correlation (P < .05) was observed with each contrast medium between K-PS and the histologic microvascular density (MVD), an angiogenesis indicator. Despite the considerable difference in molecule and particle sizes, no significant difference was observed in the MR imaging-derived mean permeability values generated with the two contrast media. CONCLUSION: USPIO, a macromolecular particulate MR imaging contrast agent, can be applied successfully to characterize tumor microvessels in animals. USPIO-derived K-PS correlated strongly with histopathologic tumor grade, MVD, and K-PS values derived by using albumin-(Cd-DTPA)(30) in the same tumors.