ASSESSING TUMOR ANGIOGENESIS USING MACROMOLECULAR MR-IMAGING CONTRAST-MEDIA

MRI enhanced with a macromolecular contrast medium (MMCM) has previous ly been shown to estimate tumor microvascular characteristics that cor relate closely with histologic microvascular density, an established s urrogate 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 ra ts xenografted with a human breast carcinoma (MDA-MB-435) were imaged after administration of albumin-gadolinium diethylenetriamine pentaace tic acid (Gd-DTA(30)) using a heavily T1-weighted three dimensional-sp oiled gradient-refocused acquisition in a steady-state pulse sequence before and 24 hours after treatment with anti-VEGF antibody (single do se of 1 mg). Changes in longitudinal relaxivity (Delta R1) were analyz ed using a bidirectional two-compartment kinetic model to estimate tum or fractional blood volume (fBV) and permeability surface area product (PS). Data showed a significant decrease (P < .05) of tumor PS with r espect to macromolecular contrast medium at 24 hours after treatment w ith anti-VEGF antibody. No significant change was observed in fBV. Sup pression of tumor microvascular permeability induced by anti-VEGF anti body can be detected and quantified by MMCM-enhanced MRI. MRI grading of tumor angiogenesis and monitoring of anti-angiogenesis intervention s could find wide clinical application.