Assessing tumor angiogenesis using macromolecular MR imaging contrast media

Abstract

MRI enhanced with a macromolecular contrast medium (MMCM) has previously been shown to estimate tumor microvascular characteristics that correlate closely with histologic microvascular density, an established surrogate of tumor angiogenesis. A similar MMCM‐enhanced MRI technique has now been used to investigate the acute tumor microvascular effects of antibody‐mediated inhibition of vascular endothelial growth factor (VEGF), a well‐studied and potent angiogenesis stimulator. Athymic rats xenografted with a human breast carcinoma (MDA‐MB‐435) were imaged after administration of albumin‐gadolinium diethylenetri‐amine pentaacetic acid (Gd‐DTPA 30) using a heavily TI‐weighted three dimensional‐spoiled gradient‐refocused acquisition in a steady‐state pulse sequence before and 24 hours after treatment with anti‐VEGF antibody (single dose of 1 mg). Changes in longitudinal relaxivity (ΔR1) were analyzed using a bidirectional two‐compartment kinetic model to estimate tumor fractional blood volume (fBV) and permeability surface area product (PS). Data showed a significant decrease (P < .05) of tumor PS with respect to macromolecular contrast medium at 24 hours after treatment with anti‐VEGF antibody. No significant change was observed in fBV. Suppression of tumor microvascular permeability induced by anti‐VEGF antibody can be detected and quantified by MMCM‐enhanced MRI. MRI grading of tumor angiogenesis and monitoring of anti‐angiogenesis interventions could find wide clinical application.