Ultrasound technology, typically used in radiology for imaging studies, is showing potential for augmenting breast cancer treatment by increasing oxygen levels in tumors, researchers have found.

Boosting oxygen saturation of tumors increases the effectiveness of radiation therapy that kills cancer cells, and using ultrasound to inject oxygen into tumors, tripling the sensitivity of the cancer to radiation, a new study has found.

The procedure, which pops microbubbles filled with oxygen in breast cancer tumors right before radiation therapy, has been used in preliminary studies to double the survival rates in mice, according to a new study in the International Journal of Radiation Oncology•Biology•Physics.

The approach would further expand the use of ultrasound beyond imaging and potentially opens the door to more successful cancer treatment in humans, according to the study authors.

The use of ultrasound helps burst “microbubbles” of oxygen in a tumor, right, compared with the image at left, before oxygenation.
The use of ultrasound helps burst “microbubbles” of oxygen in a tumor, right, compared with the image at left, before oxygenation.

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Radiation therapy is frequently used to treat breast cancer. The therapy works by creating oxygen and other free radicals in tumors out of the oxygen in the tissues. When oxygen levels are low, the number of free radicals produced by radiation therapy is also lower. Most solid cancer tumors contain little oxygen, in part because they quickly outgrow the supply of oxygen in blood vessels that can penetrate the tumors. The lack of oxygen makes the tumors more resistant to radiation than oxygenated tissue.

“You need a certain amount of oxygen to make radiation kill the tumors,” says John R Eisenbrey, associate professor of radiology at Thomas Jefferson University in Philadelphia and senior author of the study. Finding a way to increase oxygen levels in cancer tumors has been a goal of radiation therapy for many years, he says.

Researchers delivered oxygen-filled microbubbles to the general blood flow of mice with cancer tumors via intravenous injection. The bubbles wash into the tumor, and then disappear as they are popped locally with beams of high-intensity ultrasound to deliver oxygen to the tumor, raising the oxygen levels in the tumor tissue. The researchers then immediately administered radiation therapy, the effectiveness of which was accentuated. Mice that received these microbubbles survived 76 days, compared with mice receiving a placebo, which survived only 46 days.

The researchers’ next steps are to expand the procedure to other types of cancer tumors and develop a longer time frame for the microbubbles to prolong the oxygenation because some radiation therapies take longer. The researchers are also working to expand their study to the use of microbubbles in clinical trials with humans.

"The very act of bursting these microbubbles within the tumor tissue seems to change the local physiology of the tumor and make cells generally more permeable to oxygen and potentially to chemotherapy as well," Eisenbrey says. "We think this is a promising approach to test in patients to amplify the effects of radiation therapy."

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