Gene expression assay to determine radiation exposure

Unmet Need

Ionizing radiation poses a significant risk as an environmental hazard and is linked to the development of multiple cancers in adults and children. Healthcare professionals, nuclear power plant employees, and research scientists are among those frequently exposed to ionizing radiation in the workplace. Beyond routine occupational exposure, accidents in these settings can expose individuals to higher-than-intended levels of ionizing radiation. Further, a recent US government study modeled the effect of a nuclear detonation in a major metropolitan region and has estimated that >300,000 individuals would require medical attention. In these scenarios, triaging thousands of individuals with radiation exposure is difficult as current standards, lymphocyte depletion kinetic assays and cytogenic analysis, have lengthy time-to-results compromising prompt care. Lymphocyte depletion kinetic assays track the rate of change in lymphocyte levels, a measure that directly correlates with absorbed radiation dose. This analysis is time intensive as it requires daily blood draws from patients. Separately, cytogenetic analysis identifies breaks in DNA following radiation exposure to determine absorbed radiation dose. This complicated analysis is time and labor intensive as it requires days to run and skilled laboratory personnel to execute testing and assess samples. Delaying treatment following radiation exposure can make patient outcomes significantly worse. There is a need for improved high-throughput diagnostic screening tests to accurately and rapidly identify individuals with significant exposure to ionizing radiation.

Technology

Duke inventors have developed a screening test for radiation exposure. This is intended to be used by clinicians to assess radiation exposure and interrogate exposure level. Specifically, Duke inventors have discovered a set of genes that when analyzed together predict an absorbed radiation dose. Gene expression analysis is performed by collecting whole blood, extracting RNA, and analyzing the sample for specific gene expression patterns. This test is adaptable for high-throughput screening, enabling analysis of >600 samples in less than 24 hours. Further, the time to results for this test is < 8 hours. This has been demonstrated in nonhuman primate (NHP) irradiation experiments, where the test achieved 98.5% sensitivity and 90% specificity in detecting lower-dose irradiation (2.0 Gy), and 92% sensitivity and 84% specificity for higher-dose irradiation (6.0 Gy). These findings are clinically meaningful because patients with absorbed radiation levels between 2.0 and 6.0 Gy are the most likely to benefit from prompt medical intervention, whereas those with absorbed radiation levels above 6.0 Gy have a poor clinical prognosis.

Advantages

• Amenable to high-throughput analysis with time to results in less than 8 hours (~40 hours sooner than best-case scenario gold-standard)
• Pilot testing across labs demonstrated a coefficient of variation (CV) of 11%
• Low incidence of false positives and false negatives
• Eliminates the need for special handling of blood samples