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Our findings demonstrate the potential advantages of ultrasound-triggered oxygen delivery to solid tumors and warrant future efforts into clinical translation of the microbubble platform.

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Objectives-Hypoxic cancer cells have been shown to be more resistant to radiation therapy than normoxic cells. Hence, this study investigated whether ultrasound (US)-induced rupture of oxygen-carrying microbubbles (MBs) would enhance the response of breast cancer metastases to radiation.Methods-Nude mice (n = 15) received stereotactic injections of brain-seeking MDA-MB-231 breast cancer cells into the right hemisphere. Animals were randomly assigned into 1 of 5 treatment groups: no intervention, 10 Gy radiation using a small-animal radiation research platform, nitrogen-carrying MBs combined with US-mediated MB rupture immediately before 10 Gy radiation, oxygencarrying MBs immediately before 10 Gy radiation, and oxygen-carrying MBs with US-mediated MB rupture immediately before 10 Gy radiation. Tumor progression was monitored with 3-dimensional US, and overall survival was noted.Results-All groups except those treated with oxygen-carrying MB rupture and radiation had continued rapid tumor growth after treatment. Tumors treated with radiation alone showed a mean increase in volume AE SD of 337% AE 214% during the week after treatment. Tumors treated with oxygen-carrying MBs and radiation without MB rupture showed an increase in volume of 383% AE 226%. Tumors treated with radiation immediately after rupture of oxygen-carrying MBs showed an increase in volume of only 41% AE 1% (P = 0.045), and this group also showed a 1 week increase in survival time.Conclusions-Adding US-ruptured oxygen-carrying MBs to radiation therapy appears to delay tumor progression and improve survival in a murine model of metastatic breast cancer.B reast cancer is the most common of all cancers among women, projected to affect more than 12% of women in the United States. 1 Although several treatment options are available for early-stage breast cancer, they are more limited once the tumor becomes metastatic. This is particularly critical for metastasis to the brain, for which focused radiation therapy is the main treatment method. 2 It has been documented that metastasis is linked to tumor angiogenesis, especially in aggressive breast cancers. [3][4][5] The rapid and chaotic process of tumor angiogenesis