Abstract

To determine the effects of ultrasound exposure in the presence of microbubble contrast agent (SonoVue) on the subcutaneous tumor of nude mice. Nude mice bearing subcutaneous tumor were prepared and treated with ultrasound. These animals were divided into three groups: control group (without treatment), low-frequency ultrasound group (US) and low-frequency ultrasound  contrast agent group (US+UCA). UCA was microbubble contrast agent (SonoVue). The tumors were exposed to pulsed ultrasound with a 40% duty cycle and an intensity of 26 MW/cm² at a frequency of 20 kHz for 3 min using a digital sonifier once every other day for two weeks. The damage to vascular endothelial cells was assessed via transmission electron microscopy (TEM). The protein expressions of VEGF and COX-2 of vessels were detected by Western blot assay. The percentage of tumor shrinkage in US UCA group was higher than US group and down-regulation of VEGF and COX-2 were detected in US  UCA group. After treatment, degeneration of endothelial cells, mitochondrial vacuolation and lumen occlusion were observed in the tumor of US  UCA group. These changes were seldom observed in the US group. Low-frequency ultrasound in the presence of contrast agent may exert therapeutic effect on subcutaneous tumor through destruct of the blood vessels in the tumor.

Key words: Ultrasonic biophysics, low-frequency, contrast agent, cavitations, thermal mechanism.