U.S. Agency Selects Rochester for Radiation Research Contract

March 02, 2010

The University of Rochester Medical Center has received a $3.9 million one-year contract, with options to increase to a total of $42 million over the next four years, to develop a simple, quick blood test to measure radiation exposure after an act of terrorism or nuclear accident.

The project is funded by the Biomedical Advanced Research and Development Authority (BARDA), within the Office of the Assistant Secretary for Preparedness and Response in the U.S. Department of Health and Human Services. http://www.hhs.gov/aspr/

The URMC was one of nine institutions to win BARDA awards, totaling $35 million for the first year and up to $400 million over five years.

Principal investigator Bruce Fenton, Ph.D., URMC professor of Radiation Oncology, explained that scientists currently have the ability to detect radiation exposure in people, but the process is cumbersome. It requires drawing blood, takes at least two days for the culture to properly show chromosomal damage, and demands special expertise to analyze and score the sample.

“In a mass-casualty situation where potentially hundreds or thousands of people are exposed to radiation,” Fenton said, “we would need a system that is more rugged and field-ready. Ideally it would require no special calibration or user skills, and could provide a measurement within 24 hours with just a drop of blood from a finger prick obtained within 24 to 48 hours after exposure.”

High levels of ionizing radiation can be lethal, especially when the entire body is exposed. If the bone marrow is irradiated, it destroys the body’s ability to produce infection-fighting white blood cells. During the first four to 48 hours after exposure, cells die rapidly and spill DNA into the bloodstream.

Therefore, if scientists could precisely measure the radiation-induced DNA in blood plasma, it would provide a clearer picture of the level of exposure and potential harm. Fenton and co-investigator Steven Swarts, Ph.D., assistant professor of Radiation Oncology, will lead a team to test the accuracy of a novel biomarker, which was first used to detect trace levels of a specific DNA sequence in the laboratories of Lurong Zhang, M.D., Ph.D., also a professor in the Department of Radiation Oncology.

Preliminary investigations showed that for a single cell killed by radiation more than a million copies of the biomarker are released into the bloodstream. Having such an enormous level of the biomarker present in the blood should make it possible to quickly identify people who have been exposed to radiation.

The second phase of the project involves developing a portable instrument for first responders and emergency personnel that could be used to triage patients. In an emergency it would be important to distinguish non-exposed people and those who have survivable exposure, from people who received higher doses or a lower dose coupled with another serious risk, the scientists said. The URMC will be working with an Australia-based company, Invetech, to adapt a hand-held dosimeter that could provide such information.

Researchers also have designed a clinical trial to collect supporting data for the genomic changes they have seen in preliminary lab investigations. The trial results could have broader implications for people receiving radiation therapy for cancer. Enrollment will consist of URMC patients who require significant radiation as part of their regular treatment plan. Those patients will be asked to submit blood samples, which will be analyzed for genomic changes in response to radiation therapy. If the blood work showed a large amount of the novel biomarker, for example, it might indicate a good tumor response to therapy, researchers said.

Some local job growth can be attributed to the BARDA award. Project leaders have already filled nearly 10 new positions for lab technicians, administrators, researchers and a clinical regulatory manager, and they expect to hire at least five more research scientists in the future, Fenton said.

The new BARDA contract is the second to the URMC. In 2008 the government anti-terrorism agency awarded $3 million to a team led by Yuhchyau Chen, M.D., Ph.D., to study drugs that might offset the harmful effects of radiation exposure. That contract has been extended, and comes up for renewal later this year.

In addition to Fenton, Swarts and Zhang, co-investigators for the new project include: Michael Milano, M.D., Ph.D., assistant professor of Radiation Oncology who will direct the clinical studies; and Paul Okunieff, M.D., adjunct professor of Radiation Oncology and former department chair, who recently left URMC after being named director of the University of Florida Shands Cancer Center. He will remain as co-principal investigator.

BARDA provides a comprehensive approach to research and development for public health medical emergencies. Its portfolio includes building infrastructure for vaccines, drugs, therapeutics, diagnostic tools and other products for emergencies such as chemical, biological, radiological and nuclear threats, and pandemic influenza and emerging infectious diseases.

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