Use of VEGFR-2 targeted ultrasound contrast agent for the early evaluation of response to sorafenib in a mouse model of hepatocellular carcinoma.

The aim of this study was to assess the early response to sorafenib using ultrasound molecular imaging in a murine model of hepatocellular carcinoma (HCC). A xenograft model of HCC was established. Then, mice were divided in two groups and received treatment (sorafenib) or placebo for 14 days. The treatment group was further divided into non-responders and responders according to the degree of growth. Contrast enhanced ultrasound (CEUS) was performed using VEGFR-2 targeted microbubbles (BR55, Bracco Suisse SA, Geneva, Switzerland). Dedicated software was used to quantify the amount of bound microbubbles in the tumor as a numerical value (differential targeted enhancement (dTE)). Tumors were then excised and western blot analysis performed. The dTE values decreased from day 0 to day +14 both in the treatment and control groups, but were lower in the former. The non-responder group had higher dTE levels at day 2 compared to responders (p = 0.019). BR55 appears to be useful in the prediction of response to sorafenib in a xenograft model of HCC.