Potentiation of Chemotherapy by Low-level Ultrasound

Abstract

We have performed in vitro and in vivo tests to determine whether ultrasound (US) at levels lower than previously investigated by others could still potentiate chemotherapeutic cell killing. Positive results were obtained with adriamycin and diaziquone. Two types of low-level US were effective: tone-burst US (10% duty cycle, 1.765 MHz, ISATA = 0.25 W/cm2), and pulsed US (2.5 MHz centre frequency, 1 kHz repetition frequency, MPa-level pressure amplitudes), distributed uniformly over the biological target. These US beams were non-cytotoxic and produced negligible temperature elevation. Statistically significant US-induced increases in drug cytotoxicity were observed in CHO and MCF-7 WT but not V79 cells for 1-h drug exposures at several drug concentrations. The effects of combined drug and US treatments in vivo were studied by measuring post-treatment volume changes in uterine cervical squamous cell carcinoma implanted in the cheek pouch of the Syrian hamster. A statistically significant US-drug synergy in tumour volume reduction was observed with adriamycin and diaziquone.