Molecular ultrasound imaging of tumor response to bevacizumab using a breast cancer animal model

Abstract

Ultrasound (US) contrast agents, or microbubbles (MBs), have shown immense potential in cancer detection, staging and monitoring drug treatment. Contrast-enhanced US imaging utilizes non-linear oscillations of MBs to improve signal detection from the vasculature. Targeted MBs to over-expressed receptors in a region-of-interest allow enhancement of intratumoral visualization of vasculature. This permits longitudinal studies of angiogenesis development and shows potential in analyzing tumor response to therapy. In this study, breast cancer-bearing mice were analyzed using molecular US imaging for early response to bevacizumab, a vascular disrupting agent. Mice were injected systemically with MBs targeted simultaneously to VEGFR2, p-selectin and α <sub xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">V</sub> β <sub xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">3</sub> . Mice underwent molecular US imaging and were analyzed for changes in intratumoral enhancement after delivery of bevacizumab. Individual animal response to therapy was analyzed and established as a 10% or greater reduction in intratumoral enhancement by day 3 post therapy. Intratumoral enhancement was assessed using custom Matlab software. Therapeutic group animals showed a significant response to drug compared to the control group by day 3 (P <; 0.01). Molecular US imaging is a non-invasive, inexpensive approach for analyzing early response to vascular disrupting agents as demonstrated by this study in a breast cancer animal model.