Award Number: W81XWH-08-1-0479 TITLE: Treatment of breast tumors using pulsed HIFU for delivery and activation of sonosensitizers PRINCIPAL INVESTIGATOR:

Approved for public release; distribution unlimited Distribution limited to U.S. Government agencies only; report contains proprietary information The views, opinions and/or findings contained in this report are those of the author(s) and should not be construed as an official Department of the Army position, policy or decision unless so designated by other documentation. Public reporting burden for this collection of information is estimated to average 1 hour per response, including the time for reviewing instructions, searching existing data sources, gathering and maintaining the data needed, and completing and reviewing this collection of information. Send comments regarding this burden estimate or any other aspect of this collection of information, including suggestions for reducing Respondents should be aware that notwithstanding any other provision of law, no person shall be subject to any penalty for failing to comply with a collection of information if it does not display a currently valid OMB control number. 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.