Purpose:To evaluate the diagnostic and prognostic potential of a new protein-binding contrast medium, B22956/1, for quantitatively characterizing tumor microvessels by MRI and monitoring response to antiangiogenic therapy. Materials and Methods:Dynamic contrast-enhanced MRI (DCE-MRI) was performed in an experimental cancer model with the use of the novel protein-binding agent B22956/1, a low molecular contrast agent (ProHance™), and a macromolecular contrast medium, albumin-(Gd-DTPA). MDA-MB-435, a human cancer cell line, was implanted in 22 athymic rats. Animals were assigned randomly to a control (saline) or drug-treated (Avastin™) group. MRI was performed at baseline and after nine days of treatment. The transendothelial permeability (K PS ) and the fractional blood volume (fBV) were estimated from the kinetic analysis of dynamic MR data using a two-compartment model. Tumor growth was also measured from volumetric MRI.Results: Tumors grew more slowly, although not significantly (P ϭ 0.07), in the drug-treated group. The K PS determined for B22956/1 decreased significantly in the drugtreated group compared to baseline (P Ͻ 0.05), and progressed significantly in the control group. However, no significant changes were resolved with the use of ProHance or albumin-(Gd-DTPA). Conclusion:With the use of appropriate contrast media, the therapeutic effects of an anti-VEGF antibody on tumor microvessels can be monitored by dynamic MRI. The dynamic range of permeability to B22956/1, and the sensitivity to change of this parameter suggest a potential application in the clinical setting.

Carboxymethyldextran (CMD)-A2-Gd-DOTA, a slow clearance blood pool contrast agent with a molecular weight of 52.1 kDa, designed to have intravascular residence for more than 1 h, was evaluated for its potential to characterize and differentiate the microvessels of malignant and benign breast tumors. Precontrast single-slice inversion-recovery snapshot FLASH and dynamic contrast-enhanced MRI using an axial T1-weighted three-dimensional spoiled gradient recalled sequence was performed in 30 Sprague-Dawley rats with chemically induced breast tumors. Endothelial transfer coefficient and fractional plasma volume of the breast tumors were estimated from MRI data acquired with CMD-A2-Gd-DOTA enhancement injected at a dose of 0.1 mmol Gd/kg body weight using a two-compartment bidirectional model of the tumor tissue. The correlation between MRI microvessel characteristics and histopathological tumor grade was determined using the Scarff-Bloom-Richardson method. Using CMD-A2-Gd-DOTA, no significant correlations were found between the MR-estimated endothelial transfer coefficient or plasma volumes with histological tumor grade. Analysis of CMD-A2-Gd-DOTA-enhanced MR kinetic data failed to demonstrate feasibility for the differentiation of benign from malignant tumors or for image-based tumor grading.