Radiation Exposure Test Enables Critical, Fast Treatment

R&D DIGEST

If a catastrophic nuclear event ever occurs, a blood test that detects radiation exposure levels within 72 hours could ensure that vital patient treatment would be administered quickly. Using gene chip technology, a test developed at Duke University Medical Center (Durham, NC) scans genetic material to find certain patterns that indicate exposure to radiation. Such a tool would be crucial when time is critical.

“There isn't a practical rapid test that exists for the anticipated scenario of a dirty bomb or an improvised nuclear detonation,” says John Chute, MD, associate professor of medicine at Duke. The current cytogenetics assay that would be used in such a situation looks at damage to DNA in blood or bone marrow cells, but it takes about a week to produce results, adds Chute. Duke's test provides results in three days.

The test scans gene activity and looks for patterns that indicate uniqueness to a certain phenotype. In this case, the researchers designed the model to find a pattern that is representative of radiation exposure.

The assay consists of a gene chip that contains a small grid, an analyzer that automates sample processing, and computer analysis that compresses the information into numerical results to quantify gene activity.

The test has tremendous potency, says Chute. Researchers could examine thousands of genes that are represented in peripheral blood cells. They identified patterns of gene expression, representing 25–100 genes, which indicate radiation exposure. From the human samples, the researchers found that a group of 25 genes predicted the radiation response in humans. However, they are still working on confirming the number of genes that can give an accurate diagnosis of radiation exposure.

At the start of the test, the researchers collect a small blood sample and isolate the ribonucleic acid to develop the genetic template. The genetic material is modified and uniformly applied in microdroplets into wells in a 5 ¥ 8-cm grid. Each well represents a different gene. Fluorescent labels are used to determine which genes represented on the grid will bind the genetic material, indicating the gene of interest that is over- or underrepresented in the patient.

The test's proof of concept has been demonstrated in mice and humans. The next step is to refine the signatures of radiation to look at factors such as the effects of time, age, and gender. “We ultimately want to have the most robust signature that can reflect radiation exposure independent of all those variables,” says Chute.

Despite the encouraging data, the researchers could face hurdles in commercializing the technology, because some companies might not see an immediate patient need for it. Chute says the team is keeping an open mind in translating the technology for use in the government's national stockpile.

Another alternative is for researchers to partner with a diagnostics company in developing a quantitative real-time reverse transcriptase polymerase chain reaction (RT-PCR) test. It's possible that an RT-PCR approach could serve in a mobile capacity and produce results in just 12 hours.

“We're still at an early point in developing the technology and understanding its limits,” says Chute. “Now that we've had some preliminary success, we're starting to think about optimal ways to translate this test into one for radiation exposure.”

The National Institute of Allergy and Infectious Diseases is funding the work. Details about it were published in the April 3 edition of the journal Public Library of Science Medicine.

Copyright ©2007 Medical Device & Diagnostic Industry