Treatment of Breast Tumors using Pulsed HIFU for Delivery and Activation of Sonosensitizers

摘要

High intensity focused ultrasound (HIFU) has been combined with a Rose Bengal derivative (RB2) to provide a synergistic cytotoxicity requiring the presence of both ultrasonic cavitation and drug. In vitro tests have shown that a short treatment (less than 30s) of pulsed HIFU with power sufficient for cavitation destroys >95% of breast cancer cells in suspension with 15uM of the compound. Neither the pulsed HIFU nor the RB2 compound was found to have any impact on the viability of the cells when used alone. Introducing an antioxidant (N-acetylcysteine, NAC) reduced the effectiveness of the treatment. In vivo tests using these same cells growing as a xenograft in mice were also done. Ultrasound contrast agents were used to initiate cavitation. We were able to demonstrate rapid tumor regression for tumors with cavitation. It was not clear if the addition of the RB2 yielded any substantial improvement over the contrast agent alone. In some animals, ablating a tumor with cavitation resulted the subsequent regression of both treated and control tumors.