Studies in mice show that combining a form of ultrasound with radiation can enhance the effects of radiation, minimizing the amount of X-rays that are required for treatment and thereby minimizing the side effects. The process works on human tumors grown in mice, and the research teams hopes to begin human trials within 12 months.
The conventional assumption about radiation therapy is that it destroys tumor cells by disrupting their DNA, interfering with replication. That is certainly true, as far as it goes, according to Dr. Gregory Czarnota, a radiation oncologist at the University of Toronto’s Sunnybrook Research Institute. But a growing body of evidence indicates that the radiation also affects blood vessels feeding the tumor — the X-rays cause cells within the blood vessels to self-destruct, a process called apoptosis.
Czarnota and his colleagues reasoned that mechanical disruption of the blood vessels could accelerate this process. One way to do this might be with microbubbles, typically micro-sized spheres of a gas such as a perfluorocarbon encapsulated within a shell of a protein of lipid. The microbubbles can pass through most of the circulatory system and can be burst with pulses of ultrasound at select frequencies. Such microbubbles are already being tested to break down the blood-brain barrier to allow therapeutic agents to enter the brain, to render certain cells more permeable to drugs, and to break up blood clots. Czarnota reasoned that they could also be used to weaken blood vessels servicing tumors.
Czarnota and his team implanted human prostate tumors in mice, then treated them with either radiation alone, ultrasound alone, or a combination of the two. They reported in the Proceedings of the National Academy of Sciences that a single treatment with microbubbles/ultrasound and a 2-Grey dose of X-rays reduced tumor volume by 40% to 50%. In contrast, a single 2-Gy dose of radiation alone reduced tumor volume by about 5%, as did a single treatment with microbubbles/ultrasound alone. Normally, as many as 35 2-Gy doses of radiation are required to produce a similar amount of tumor death.
“This work has really opened up a new field of medicine,” Czarnota said. “We will be continuing to work out effects and optimal timing of the two treatments over the next year in small and large animal models.” The first application in humans, he added, will most likely be with large, recurrent chest wall tumors.
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