'Fingerstick' assay identifies exposure to toxic radiation levels

  • Yadav M & al.
  • Sci Transl Med
  • 15 Jul 2020

  • Univadis Clinical Summaries
Access to the full content of this site is available only to registered healthcare professionals. Access to the full content of this site is available only to registered healthcare professionals.

A novel test, based on biomarkers measured through a single drop of blood via a fingerstick, could give rapid results on radiation exposure levels, unlike current testing methods, which may take as long as 3-4 days to yield results.

The test would be useful for identifying radiation sickness, or acute radiation syndrome (ARS), which can cause injury to multiple organs in the body within a very short time period. While ARS is generally the result of exposure to nuclear radiation and radioactive fallouts from a nuclear weapon detonation or reactor accidents, the assay would also be relevant to patients with cancer, particularly those who have undergone bone marrow transplantation, say scientists involved in developing the test.  Any patient receiving intense radiation therapy may be at risk for overdosing as well as underdosing, they note.

"A biomarker-based evaluation has relevance for evaluation of dose-response in human patients on radiotherapy," said lead author Naduparambil Jacob, PhD, an associate professor and scientist at the Ohio State University Comprehensive Cancer Center — Arthur G. James Cancer Hospital and Richard J. Solove Research Institute in Columbus. "At least in the field of radiation therapy, in general, clinicians follow a 'one size fits for all' approach and this study brings up the concept of a possible biomarker-guided adaptive dosing."

Jacob told Medscape Medical News that in bone marrow transplant patients, this test could be used to evaluate the efficiency of marrow ablation before transplant, and marrow reconstitution after the transplant. However, the test is not yet ready for clinical use.

"Although we have shown the robustness of baseline in healthy humans and dose response and kinetics in specimens from human patients with leukemia, I want to emphasize that it is a proof-of-the concept study and the testing needs more validation before becoming available clinically," he cautioned.

Research on the novel test was published on July 15 in Science Translational Medicine.

Identifying individuals who may have been exposed to excessive radiation is essential, as exposure above a certain dose threshold requires immediate and aggressive treatment, the researchers explain. The standard test for radiation exposure is a dicentric chromosome assay, which looks for radiation-induced DNA damage, but results can take several days.

Jacob and colleagues hypothesized that radiation exposure could be estimated by comparing the relative expression of two microRNAs in the blood, which are small noncoding RNA molecules that play a role in gene regulation.

The first one is microRNA-150-5p, which Jacob and his team had identified several years ago as a biomarker to measure the extent of bone marrow damage. It is radiation sensitive and levels decline as the dose of radiation increases. The second one, microRNA-23a-3p, is unaffected by radiation and maintains its concentration after exposure.

The authors studied the response and the stability of both microRNAs to determine the feasibility of using them to assess radiation exposure at dose range and different time points. Their study used both mice and blood samples from leukemia patients before and after undergoing radiation therapy.

To investigate dose-response in humans, the authors examined changes in blood concentrations of microRNA-150-5p and microRNA-23a-3p in patients with acute myeloid leukemia (AML), acute lymphoblastic leukemia (ALL), myelodysplastic syndrome (MDS), and mixed phenotype acute leukemia (MPAL) who had received radiation-based myeloablative conditioning in preparation for a transplant.

The blood samples were collected at baseline and time points during and after the conditioning regimen. Analyses confirmed the depletion of serum concentrations of microRNA-150-5p after radiation, whereas microRNA-23a-3p remained stable.

In a statement, Jacob explained that it is impossible to look at patients and determine how much radiation they have absorbed, as the impact can be cumulative. "As a result, radiation sickness could occur weeks or months after the radiation therapy," he said. "With additional research, this new testing method could potentially help oncologists measure — in real time — absorbed radiation, and intervene before radiation sickness occurs."

Jacob and coauthor Arnab Chakravarti are coinventors on US patents related to this research and issued to the Ohio State Innovation Foundation (OSIF). These patents are under license from OSIF to an outside party. The other coauthors have disclosed no relevant financial relationships.

The article was originally published on Medscape.com.