Image-guided doxorubicin delivery with ultrasound and microbubbles in a mouse model of hepatocellular carcinoma using a diagnostic ultrasound system

Abstract

Despite advances in chemotherapeutic drug development, hepatocellular carcinoma (HCC) is still the third leading cause of cancer-related deaths worldwide with a <

30% 5-year survival rate. This poor prognosis can be attributed to the fact that HCC most commonly occurs in patients with pre-existing liver conditions, rendering many systemic options too aggressive. Patient survival rates could be improved by a more targeted approach. Ultrasound and microbubbles can provide a means for overcoming traditional barriers defining drug uptake. The goal of this work was to evaluate preclinical efficacy of image-guided drug delivery of doxorubicin with ultrasound and microbubbles. To this end, therapy settings were created on a Philips EpiQ and S5-1 phased array probe to provide focused sound for treatment. Sonovue was chosen as a clinically approved microbubble. A genetically engineered mouse model was bred and used as a physiologically relevant preclinical analog to human HCC. It was observed that ultrasound and microbubble therapy resulted in enhanced doxorubicin distribution as seen in fluorescent microscopy. Further, immediate vascular shutdown was observed in treated animals. The combination of these effects may be exploited to treat a challenging malignancy.