MRI monitoring of avastin™ antiangiogenesis therapy using B22956/1, a new blood pool contrast agent, in an experimental model of human cancer

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(TM)), 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(TM)) 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 = 0.07), in the drug-treated group. The K-PS determined for B22956/1 decreased significantly in the drug-treated group compared to baseline (P < 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. (C) 2004 Wiley-Liss, Inc.