Dynamic MRI Enhanced with Albumin–(Gd-DTPA)30 or Ultrasmall Superparamagnetic Iron Oxide Particles (NC100150 Injection) for the Measurement of Microvessel Permeability in Experimental Breast Tumors

Abstract

Characteristics of the cell nuclei within human breast tumors, as assayed and scored by the Scarff-Bloom-Richardson (SBR) histopathologic method, correlate with patient prognosis and long-term survival rates (1,2). We have shown previously in rodent mammary tumors that the histopathologic tumor grade correlates with quantitative magnetic resonance imaging (MRI)–derived estimates of tumor microvascular permeability obtained using a prototypic macromolecular contrast medium, albumin–(GdDTPA)30 (3). Microvessel permeability depends on functional and morphologic characteristics of cancer vessels and on physicochemical properties of the injected solute/ contrast medium molecule (4–7). In this study, we focus on specific characteristics of two contrast media and their influence on MRI-derived estimates of microvessel characteristics. The increased permeability of tumor vessels to macromolecular solutes has been demonstrated repeatedly using albumin–(Gd-DTPA)30, which is used in this study as a reference standard (8–10). Although not previously tested as probes of endothelial hyperpermeability, ultrasmall superparamagnetic iron oxide (USPIO) particles, having a mean diameter of approximately 20 nm, were compared in this study to albumin–(Gd-DTPA)30, which is approximately 20% the size of USPIO. Unlike albumin–(Gd-DTPA)30, which is incompletely eliminated and potentially immunogenic, USPIO particles have a favorable pharmacologic and tolerance profile and are now being tested clinically (11). Thus, the purpose of this study was to define the potential of USPIO (represented by NC100150 Injection [Nycomed Imaging AS, Oslo, Norway]) for the quantitative characterization of tumor microvasculature, specifically for measures of the microvessel permeability and the plasma volume. Results were compared to estimates derived with the established macromolecular contrast medium, albumin–(Gd-DTPA)30, and to the histologic tumor grade.