Oncoscience

Breast tumor response to ultrasound mediated excitation of microbubbles and radiation therapy in vivo

Priscilla Lai3,4, Christine Tarapacki1,2,3, William T. Tran1,3, Ahmed El Kaffas1,2,3, Justin Lee1,2,3,4, Clinton Hupple1,23, Sarah Iradji3,4, Anoja Giles1,3, Azza Al-Mahrouki1,3 and Gregory J. Czarnota1,2,3,4

1 Radiation Oncology, Sunnybrook Health Sciences Centre, Toronto, Ontario, Canada

2 Department of Radiation Oncology, University of Toronto, Toronto, Ontario, Canada

3 Imaging Research, Sunnybrook Health Sciences Centre, Toronto, Ontario, Canada

4 Department of Medical Biophysics, University of Toronto, Toronto, Ontario, Canada

Correspondence:

G. J. Czarnota, email:

Keywords: Microbubbles, high frequency ultrasound, microvasculature, radiation, breast neoplasm

Received: January 13, 2016 Accepted: March 01, 2016 Published: April 02, 2016

Abstract

Acoustically stimulated microbubbles have been demonstrated to perturb endothelial cells of the vasculature resulting in biological effects. In the present study, vascular and tumor response to ultrasound-stimulated microbubble and radiation treatment was investigated in vivo to identify effects on the blood vessel endothelium. Mice bearing breast cancer tumors (MDA-MB-231) were exposed to ultrasound after intravenous injection of microbubbles at different concentrations, and radiation at different doses (0, 2, and 8 Gy). Mice were sacrificed 12 and 24 hours after treatment for histopathological analysis. Tumor growth delay was assessed for up to 28 days after treatment. The results demonstrated additive antitumor and antivascular effects when ultrasound stimulated microbubbles were combined with radiation. Results indicated tumor cell apoptosis, vascular leakage, a decrease in tumor vasculature, a delay in tumor growth and an overall tumor disruption. When coupled with radiation, ultrasound-stimulated microbubbles elicited synergistic anti-tumor and antivascular effects by acting as a radioenhancing agent in breast tumor blood vessels. The present study demonstrates ultrasound driven microbubbles as a novel form of targeted antiangiogenic therapy in a breast cancer xenograft model that can potentiate additive effects to radiation in vivo.


PII: 299