Researchers have developed a simple finger-prick test that scans a single drop of blood to rapidly determine whether the body has been exposed to toxic levels of radiation.
Catastrophic radiological events — like nuclear detonations — can threaten massive populations with acute radiation syndrome, which wreaks havoc on the gastrointestinal system and destroys bone marrow, leading to infections and internal bleeding. In preparation for the possibility of such a public health disaster, scientists at Ohio State have devised a speedy and scalable method for estimating radiation exposure. They published their proof-of-concept research, conducted in mice, Wednesday in Science Translational Medicine.
Timing is key when it comes to assessing radiation dosage in members of an exposed population. Victims above a certain dose threshold require immediate and aggressive treatment, such as a blood transfusion or cytokine therapy.
“Early detection will save lives,” said Naduparambil Jacob, senior author of the study and a molecular biologist at Ohio State University Comprehensive Cancer Center.
The current “gold standard” test for radiation exposure is a dicentric chromosome assay, which looks for hallmarks of radiation-induced DNA damage. The problem is that this test takes around three or four days to yield results — a waiting period that can make it harder for clinicians to know how to proceed and can potentially jeopardize patient outcomes.
“If it takes you four days to get the result, then it’s not helpful in immediate management,” said C. Norman Coleman, a researcher at the National Cancer Institute who was not involved with the study. “The idea of getting some kind of number pretty quickly that tells you what you need to do is useful for the medical system and also for the patient.”
The test Jacob’s team developed has the capability to turn out a number within hours.
It does so by harnessing two key biomarkers in the blood: miR-150-5p and miR-23a-3p, both of which are small, non-coding types of RNA molecules. The first type is known to be radiation sensitive, meaning that its levels drop as the radiation dose climbs. The second type is radiation insensitive, so its concentration remains stable despite radiation exposure.
Jacob and his colleagues hypothesized that they could estimate how much a radiation a person was exposed to by comparing the levels of miR-150-5p and miR-23a-3p after that exposure.
To test out this theory, they exposed mice to varying levels of radiation and then periodically sampled their blood to keep track of how levels of miR-150-5p changed compared to the stable miR-23a-3p. Just 6 hours after irradiation — and up until a week later — a comparison of the two biomarkers turned out to be a sensitive proxy for the radiation dosage a given mouse had undergone.
The central principle held in humans, too. Looking at blood samples from leukemia patients before and after they underwent radiotherapy treatment, the researchers confirmed that miR-150-5p levels dipped after radiation exposure, while miR-23a-3p stayed steady.
Jacob emphasized, however, that the work is still in the early stages. He said the dose estimation algorithm they built out with data from mice will have to undergo calibration in future studies on non-human primates.
Coleman said this paper represents the constant, “behind the scenes” preparation scientists undertake for potential public health disasters — whether biological, chemical, or nuclear.
Though a crisis like Covid-19 may monopolize the public’s attention, there are always scientists “in the background” gearing up for the next big disaster, he said — no matter how unlikely it might be.
Beyond preparing physicians to triage and treat patients implicated in a potential nuclear detonation, the finger-prick test has an application that’s even more far out there – all the way in outer space.
Jacob said that the test — which was developed with funding from NASA and the Department of Defense — may be deployed on space missions, since astronauts are exposed to radiation from “explosive” and “unexpected” solar flare-ups. And closer to home, he added, physicians could one day use the test to better adjust dosing when they administer radiotherapy to cancer patients.
“In 2013 we published a paper showing the origin of discovery of this combination of two molecules,” Jacob concluded. “[This is] a productization of that basic science discovery. I’m very excited. I’m very glad that I was able to contribute.”