IARPA program will enable improved quantification of low-dose ionizing radiation exposures
TEI-REX Program Virtual Proposer’s Day to be held 29 September
Most biodosimetry approaches rely upon calculating damage done to DNA or the downstream effects of irradiative damage.
The goal of the Targeted Evaluation of Ionizing Radiation Exposure (TEI-REX) program, a research and development effort from the Department of Defense Intelligence Advanced Research Projects Activity (IARPA), is to establish novel biodosimetry approaches to effects from low-dose radiation done to other biological components, specifically those which are long lasting and directly attributable to the initial ionizing insult. Sample types targeted include skin, hair, nails, sweat, natural surface oils, saliva, dermal interstitial fluid, and/or mucosal cells from the mouth.
The TEI-REX program will consider platforms capable of discovery and detection of signatures from minimally to non-invasive samples; examples of potential or demonstrated signatures associated with ionizing radiation exposure; and examples or demonstrations of models for quantifying signatures associated with radiation absorption and the exposure environment.
The key challenge associated with this effort is the identification of signatures from low-dose exposures. Lower doses of ionizing radiation will result in fewer molecular changes compared to high-dose exposures, making detection even more difficult as low-dose exposures approach ambient background, but the changes will still be present.
The higher ranges identified in IARPA’s effort (near natural baseline to 10 to 15 Gy) are aimed to be threshold measurements and signatures acting as demonstration of feasibility to capture these signatures at non-cosmic dose ranges. Evidence of amino acid and peptide sensitivities to extremely high levels of ionizing radiation, >10kGy, has been published and is currently investigated within the astrobiology community – these ranges are not of interest to this program.
The current ‘gold standard’ for biodosimetry is the dicentric chromosome assay (DCA). In use for decades with validated protocols, DCA assays can reproducibly evaluate low- and high- dose exposures (~0.1 – ~15 Gy), can be integrated into automated screening, and can perform qualitative evaluation of partial body exposures.[1-5]
More recently developed biodosimetry approaches include analyses of lymphocyte cell depletion, protein-based DNA repair responses, gene expression profiling, and micro-RNA profiling.[6-10] While these methods have demonstrated utility for specific use cases, they are heavily dependent upon transient signatures and often require baseline evaluation to accurately quantify exposure.[11-13] In addition, these methods rely on secondary or tertiary biomarkers from the actual ionizing energy or free radical effects, provide limited information on the exposure environment, and mostly require invasive or serial sampling (i.e. multiple blood draws).
Advancements across multiple technical fields over the past decade provides the opportunity to research and develop new biodosimetry methods to overcome the shortcomings of current approaches. Such advancements include novel or improved analytical methodologies or platforms; expanded knowledge space associated with the impact of ionizing radiation to target tissues; and computational techniques to enabling detection of signatures from the background noise.[14-17] Further research into this field, leveraging these advances, will enable development of new approaches for discovery, detection, and analysis of biomarker signatures associated with ionizing radiation exposure and enable improved protection of individuals who are accidentally or professionally exposed, especially at sub-clinical doses.[18,19]
Proposer’s Day – Targeted Evaluation of Ionizing Radiation Exposure (TEI-REX)
IARPA will hold a virtual Proposers’ Day meeting on September 29, 2021 with potential overflow into September 30 in order to introduce the research requirements for the TEI-REX program and provide information on program objectives.
Proposers’ Days assist potential proposers to evaluate whether and how they might respond to the Government’s research and development solicitations and to increase efficiency in proposal preparation and evaluation.
The TEI-REX Proposers’ Day is open only to registered potential proposers, and not to the media or the general public. The meeting will be held entirely on the WebEx video conference platform, and a recorded video of the meeting will be made available to the public.
Additional details on the TEI-REX Proposer’s Day are available at SAM.gov.
RFI 21-02 Targeted Evaluation of Ionizing Radiation Exposure. Closed 19 Feb 2021.
Organ-Specific Effects of Low Dose Radiation Exposure: A Comprehensive Review Frontiers in Genetics
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9. Ghandhi SA, Shuryak I, Morton SR, Amundson SA, Brenner DJ. New Approaches for Quantitative Reconstruction of Radiation Dose in Human Blood Cells. Sci Rep. 2019 Dec 5;9(1):18441. doi: 10.1038/s41598-019-54967-5. PMID: 31804590; PMCID: PMC6895166.
10. Minkoff BB, Bruckbauer ST, Sabat G, Cox MM, Sussman MR. Covalent Modification of Amino Acids and Peptides Induced by Ionizing Radiation from an Electron Beam Linear Accelerator Used in Radiotherapy. Radiat Res. 2019 May;191(5):447-459. doi:10.1667/RR15288.1. Epub 2019 Mar 8. PMID: 30849023; PMCID: PMC6506356.
11. Sullivan JM, Prasanna PG, Grace MB, Wathen LK, Wallace RL, Koerner JF, Coleman CN. Assessment of biodosimetry methods for a mass-casualty radiological incident: medical response and management considerations. Health Phys. 2013 Dec;105(6):540-54. doi: 10.1097/HP.0b013e31829cf221. PMID: 24162058; PMCID: PMC3810609.
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14. Monson KL, Ali S, Brandhagen MD, Duff MC, Fisher CL, Lowe KK, Meyer CE, Roberts MA, Tom KR, Washington AL 2nd. Potential effects of ionizing radiation on the evidentiary value of DNA, latent fingerprints, hair, and fibers: A comprehensive review and new results. Forensic Sci Int. 2018 Mar;284:204-218. doi: 10.1016/j.forsciint.2018.01.012. Epub 2018 Jan 31. PMID: 29408730.
15. Liu M, Zhang J, Wang Y, Xin C, Ma J, Xu S, Wang X, Gao J, Zhang X, Yang S. Non-invasive proteome-wide quantification of skin barrier-related proteins using label-free LC-MS/MS analysis. Mol Med Rep. 2020 May;21(5):2227-2235. doi:10.3892/mmr.2020.11020. Epub 2020 Mar 11. PMID: 32186761; PMCID: PMC7115193.
16. Cristina Cherubini, Ornella Ursini, Franco Cataldo, Susana Iglesias-Groth, & Maria Elisa Crestoni (2014). Mass spectrometric analysis of selected radiolyzed amino acids in an astrochemical context. Journal of Radioanalytical and Nuclear Chemistry, 300(3), 1061-1073.
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Sources: IARPA, Defense.gov, SAM.gov, edited by Global Biodefense.