Assessing breast cancer response to bevacizumab using contrast-enhanced ultrasound: Initial results using a murine model

This paper describes preliminary results in a murine model devoted to monitoring breast cancer response to bevacizumab therapy using contrast-enhanced ultrasound (US). Twenty mice were implanted with 2LMP breast cancer cells. Three weeks thereafter, 10 mice were administered a 0.1 mg i.p. injection of bevacizumab whereas the remaining mice received saline injections. Using a Philips iU22 scanner equipped with an L9-3 transducer, baseline and follow-up imaging at day 6 was performed using contrast-enhanced US and flash-replenishment techniques. Contrast agent flow (i.e., time-intensity curves) and tumor reperfusion parameters were derived from US image sequences and a given region-of-interest (ROI). Experimental results showed reperfusion metrics were greater for tumors treated with bevacizumab compared to controls. Significant differences found in the AUC (p < 0.01) and Ipk (p < 0.01) time-intensity curve parameters maybe due to a reduction in intratumoral pressures and restored tumor flow. No significant differences were found between control and treated tumors for either the Tpk parameter (p = 0.20) or tumor size (p = 0.18). Histological results revealed increased microvessel density (MVD) for control tumors (p < 0.01) when compared to treated mice. No significant differences in tumor necrosis levels (p = 0.18) were found between control and therapy tumor groups. Overall, these preliminary experiments demonstrate that changes in tumor vascularity and perfusion kinetics in response to antiangiogenic therapy can be distinguished using contrast-enhanced US techniques.