Abstract
Ultrasound-targeted microbubble destruction (UTMD) has been widely applied to enhance chemotherapy of tumors, yet few studies have focused on the metastatic potential induced by UTMD. This study aimed to explore the metastasis of VX2 tumors after treatment with UTMD and chemotherapy. Forty-four New Zealand rabbits bearing subcutaneous VX2 tumors were enrolled for the treatment of UTMD with chemotherapy. For UTMD, the tumors were insonated using two pulsing protocols of diagnostic ultrasound (DUS, VINNO and ECARE) with a mechanical index (MI) of 0.29-0.33, tone burst of 8.0 cycles, and frequencies of 3-4MHz. A total dose of 2ml SonoVue® was injected intermittently during 10-min UTMD exposure. The combination therapy was treated using doxorubicin (DOX, 2mg/kg) and DUS, while the tumors treated using DOX only served as the control. Tumor size was measured using the tumor volume formula. Survival time was observed until animal death or the end of the study (120days). Specific organs (lung, liver, kidney, and brain) were removed for metastatic evaluation. There were no statistical differences in overall metastasis classification and individual organ metastases among all groups (P>0.05). The tumor growth rate only showed inhibition on the 5th day (P<0.01). The survival time did not demonstrate any significant difference between UTMD and chemotherapy only (P>0.05). UTMD using long-pulse DUS with commercial microbubbles did not pose a risk of metastasis enhancement in DOX chemotherapy.
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