The Anti-Angiogenic Effects of a Vegf Decoy Receptor Can Be Monitored In Vivo Using Contrast-Enhanced Ultrasound Imaging

摘要

The development of anti-angiogenic therapies has stimulated interest in non-invasive imaging methods to monitor response. We investigated whether the effects of a vascular endothelial growth factor decoy receptor (VEGF Trap; Regeneron Pharmaceuticals, Tarrytown, NY) could be monitored in vivo using contrast-enhanced ultrasound (CEUS). Twenty nude mice (in two groups) were implanted with a human melanoma cell line (DB-1). The active group received VEGF Trap (4×25mg/kg over 2 weeks), while the control group received an inactive protein. An ultrasound contrast agent was injected followed by power Doppler imaging (PDI) and pulse inversion harmonic imaging (PIHI; regular and intermittent). Specimens were sectioned in the same planes as the images and stained for endothelial cells (CD31), cyclooxygenase-2 (COX-2), VEGF and hypoxia (Glut1). Measures of tumor vascularity obtained with the different imaging modes were compared to immunohistochemical markers of angiogenesis. Mean tumor volume was smaller in the active than in the control group (656±225 vs 1160±605mm³). Overall, PDI and VEGF correlated (r=0.34; p=0.037). Vascularity decreased from control to treated mice with intermittent PIHI as did the expression of CD31 and COX-2 (p≤0.02), while VEGF increased (p=0.05). CEUS appears to allow in vivo monitoring of the anti-angiogenic effects of VEGF Trap in the DB-1 human melanoma xenograft model.