Using biodosimetry to enhance the public health response to a nuclear incident

Abstract

Radiation Biodosimetry is a continually developing clinical diagnostic field, which focuses on biological markers that proportionally change in relationship to the amount of ionizing radiation absorbed. Examples of host marker response include changes in white cell count, specific proteins in circulation, RNAs in white blood cells, or chromosome fidelity in affected lymphocytes. Measurements of radiation biomarkers correlate with the approximate radiation dose absorbed and indirectly provide an assessment of the likelihood of developing acute radiation syndrome. The aim of this review is to summarize four biodosimetry programs that are in advanced development, later pipeline stages with funding from the Biomedical Advanced Research and Development Authority (BARDA), an agency under the Assistant Secretary for Preparedness and Response (ASPR) in the U.S. Department of Health and Human Services (HHS). With BARDA financial support, biodosimetry diagnostic assays in development will inform patient management, improve health and psychosocial outcomes, and save lives after a nuclear disaster. These tests include an SRI International developed rapid on-site screening test requiring only a finger stick of blood to triage those who have received little or no radiation from those who have received clinically significant levels of radiation and need further immediate patient management. In addition, multiple laboratory-based, high-throughput quantitative tests, currently under development by MRIGlobal, DxTerity, and ASELL, will more accurately define dose levels and possibly predict cellular and organ-damage and other longer-term effects of radiation. In the future, when clinical and analytical validation of these assays is complete, the data is reviewed by the FDA, and agency use status is obtained, rapid triage and laboratory-based biodosimetry test results will enable emergency medical teams to do the most good for the largest number of people after a nuclear blast.

United States medical preparedness for nuclear and radiological emergencies

“…As of this writing, no biodosimetry approaches have yet been cleared by the US FDA for use in radiation mass casualty triage. USG investments in biomarker discovery and device design spans exploratory studies into novel markers, through funding of more standard cytogenetic and “omics” technologies, to advanced development of prototypes and validation of biomarker panels [ 56 ]. In advanced development, there are many challenges involved in identifying laboratories and instrumentation and ensuring safe transport of samples and reagents [ 42 , 56 ].…”

Assessment and treatment requirements of public hospitals to radiation emergencies

“…Radiation biodosimetry is a continually developing field, which focuses on specific clinical and laboratory biological markers, whose values express known relationship to the absorbed dose of ionizing radiation [4]. The field of radiation biodosimetry starts from hospital triage and emergency treatment and extends to mass screening and managing large-scale population exposures to unknown levels of radiation [5,6].…”

Transcriptomics of Wet Skin Biopsies Predict Early Radiation-Induced Hematological Damage in a Mouse Model

“…Currently, there is no FDA-approved test enabling an accurate assessment of an absorbed radiation dose [ 5 ] or dosimetric measurement of IR exposure. Lack of such tests or tools delays patients’ evaluation, triage, and the identification of the best treatment strategy and outlining of ideal resources deployment [ 9 , 10 , 11 , 12 ] in a radiation-exposure event.…”

“…Realizing these challenges, the Biomedical Advanced Research and Development Authority (BARDA) is supporting the development of four products for the measurement of an absorbed radiation dose. One or more of these products is anticipated to aid in improving the outcome of care ensuing a nuclear or radiation occurrence [ 9 ]. The products are diverse in their approaches and include the following: (1) a protein-based assay that interrogates a panel of three plasma proteins, namely the salivary α amylase 1A (AMY1A), the Fms-related tyrosine kinase 3 ligand (FLT3L), and the monocyte chemotactic protein 1 (MCP1), which are modulated by radiation in a dose-dependent fashion; (2) an mRNA-based approach aimed at detecting panels of 12 or 15 radiation-sensitive mRNA molecules in blood using qRT-PCR; (3) ligation to contiguous amplified DNA fragments; (4) a cytokinesis-block micronucleus (CBMN) assay [ 13 ] aimed at detecting the dose-dependent induced micronuclei in lymphocytes [ 14 , 15 , 16 ].…”