Enhanced antitumor efficacy of ultrasonic cavitation with up-sized microbubbles in pancreatic cancer
OBJECTIVE To explore the feasibility of disrupting tumor microcirculation by the cavitation of microbubbles enhanced ultrasound (US) and analyze its pathological mechanism. METHODS Twenty-four SD male rats with subcutaneously transplanted Walker-256 tumor were divided into 3 groups, i.e. ultrasound plus microbubbles group (US + MB), US group and sham group. Pulsed US was delivered to tumor for 3 minutes during an intravenous infusion of microbubbles at 0.2 ml/kg in the US + MB group. The control groups received only the US exposure or the MB injection. Tumor perfusion was visualized with contrast enhanced ultrasound before and 0 min after treatment. Finally the pathological examination was performed. RESULTS The contrast perfusion of Walker-256 tumors vanished immediately after treatment in the US + MB group and the gray scale value (GSV) decreased from 121 ± 12 (pre-treatment) to 81 ± 9 (post-treatment, P < 0.01). There was no significant difference of GSV before and after treatment in two control groups (P > 0.05). The GSV values were 112 ± 14 and 111 ± 12 pre-treatment and 113 ± 14 and 103 ± 13 post-treatment in the sham and US groups. The pathological examination showed remarkable hemorrhage, endothelial injuries, increased intercellular edema and in situ thrombosis. CONCLUSION Microbubble-enhanced ultrasound can significantly disrupt tumor vasculature and block its circulation. And it may become a novel physical anti-angiogenetic therapy for tumor.