Researchers at MIT have devised a new method for examining how radiation damages normal tissue in the body. The knowledge may make it possible to reduce side effects for cancer patients or to develop treatments for radiation exposure.
About 50 percent of all cancer patients are treated with radiation therapy, either alone or in combination with some other type of treatment. Radiation can be very effective in killing tumor cells, but it also kills normal tissues nearby. In the gastrointestinal (GI) tract, this killing of normal cells can cause such side effects as nausea or diarrhea within days or weeks of treatment, and serious GI tissue damage can occur months or years later.
"The long-term effects that occur six months to a year or more after exposure aren't reversible like the short-term ones, and they are a big unknown," said Associate Professor Jeffrey A. Coderre of MIT's Department of Nuclear Science and Engineering. The damage is similar to scar tissue formation and can seriously affect tissue function in the GI tract.
"We've come up with a tool to selectively irradiate blood vessels to study how radiation damages normal tissue over both the short term and the long term," said Coderre, who is co-author of an article appearing online the week of Feb. 27 in the Proceedings of the National Academy of Sciences (PNAS). "This is the first time it has been possible to do this."
Conventional techniques using external radiation beams are not specific enough for this type of study. "We are selectively delivering a radiation dose to all of the cells that make up the microscopic blood vessels throughout the body," he said.
The method Coderre and his colleagues at MIT and UCLA came up with involves putting boron into a drug administered intravenously in mice, and then subjecting the animals to whole-body neutron radiation using the MIT research reactor. Individual boron atoms in the blood capture a neutron, become unstable, and immediately split in half, giving off two short-range radiations (an alpha particle and a lithium ion) in the process.
The boron is kept in the blood by trapping it inside a type of nanoparticle known as a liposome, which is only billionths of a meter in size. These particles are too big to move from the blood into normal tissues, so the short-range radiations from the boron-neutron reactions in the blood only reach the blood vessel walls and cannot damage the normal tissues outside the blood vessels.
By selectively irradiating the blood vessels, it is possible to see where the breakdown of tissue structure and function starts following radiation exposure. And that information could lead to more effective and less damaging treatments, Coderre said.
Coderre said the method can be applied to other tissues. It also has implications for the development of radioprotectors or treatments for radiation exposure. But perhaps the greatest potential is in understanding the sequence of steps that begin at the time of irradiation but take years to create damage.
For example, there will be approximately 240,000 new cases of prostate cancer diagnosed in the United States in 2006. Depending on the dose of radiation delivered to their tumor, anywhere from 20 percent to 40 percent of those patients could show some degree of late damage.
The lead author on the PNAS paper is Bradley W. Schuller, a graduate student in Coderre's lab. Peter J. Binns and Kent J. Riley, both research scientists in MIT's Nuclear Reactor Lab, also are authors on the paper, as are Ling Ma and Professor M. Frederick Hawthorne, both at UCLA.
This research was funded by the U.S. Department of Energy, the National Institutes of Health and the MIT Center for Environmental Health Sciences.
A version of this article appeared in MIT Tech Talk on March 8, 2006 (download PDF).
