Ultrasound contrast imaging of angiogenisis in a murine tumor model

Abstract

Microvascularization modifications should precede tumor size‐changes during anti‐angiogenic therapy. We applied contrast functional ultrasound imaging (fUSI) to detect changes in Wilms tumors with anti‐angiogenic treatment (Bevacizumab). Human Wilms tumor cells was grafted in left kidney of 32 mice. Once tumors had >5mm diameter, mice received : placebo, N=14; Bevacizumab for 21days, N=11; and Bevacizumab for 10days followed by placebo for 11days, N = 7. On days ‐1, +1, +9, +14 and +21 with respect to treatment start, fUSI was performed (CPS mode, SonoVue). Linear time intensity curves were obtained from regions in kidney cortex and matched‐depth of tumor for first bolus passage and 50s following acoustic destruction of contrast. Excised tumor weight decreased with increased treatment duration: 3.7+/‐1.8 g (placebo), 2.3+/‐1.9 g (Bevacizumab‐10days, placebo‐11days), 1.4+/‐0.7 g (Bevacizumab‐21 days) [p<0.05]. Area under the bolus‐passage curve (AUC) and the plateau intensity of the destruction‐reperfusion were greater from D+9 to D+21 [p<0. 04] in the placebo than Bevacizumab‐21day. For the group treated during the first 10 days, fUSI values were comparable to those of the treated group until D+14, then increased to become slightly superior to those of the placebo group by D+21. Noninvasive fUSI demonstrated revascularization after suspension of anti‐VEGF therapy.