Development of a point-of-care radiation biodosimeter: studies using novel protein biomarker panels in non-human primates

Int J Radiat Biol. 2020 Jan;96(1):35-46. doi: 10.1080/09553002.2018.1532612. Epub 2018 Nov 5.

Abstract

Purpose: There is a need to rapidly triage individuals for absorbed radiation dose following a significant nuclear event. Since most exposed individuals will not have physical dosimeters, we are developing a method to assess exposure dose based on the analysis of a specific panel of blood proteins that can be easily obtained from a fingerstick blood sample.Materials and methods: In three large non-human primate (NHP) studies, animals were exposed to single acute total body doses of x-ray or gamma radiation. A total of 895 blood samples were obtained at baseline and for 7 days after exposure, to evaluate the temporal progression of markers in each of 10 animals (5M/5F) in six dose groups receiving 0-10 Gy. We used tandem mass spectrometry and immunoassay techniques to identify radiation-responsive proteins in blood plasma samples.Results: A blood protein biomarker panel was developed based on analysis of blood plasma samples obtained from several irradiation studies in NHPs that aimed to simulate acute radiation injury in humans from a nuclear exposure event. Panels of several subsets of proteins were shown to accurately classify plasma samples into two exposure groups either above or below a critical dose threshold with sensitivities and specificities exceeding 90%.Conclusion: This study lays the groundwork for developing a radiation biodosimetry triage tool. Our results in NHPs must be compared with those in human patients undergoing radiotherapy to determine if the biomarker panel proteins exhibit a similar radiation response and allow adequate classification power in humans.

Keywords: NHP irradiation studies; Radiation biodosimetry; blood biomarkers; immunoassays; mass spectroscopy.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Biomarkers / analysis
  • Blood Proteins / analysis*
  • Hematologic Tests
  • Immunoassay
  • Macaca mulatta
  • Point-of-Care Systems*
  • Radiometry / methods*
  • Time Factors

Substances

  • Biomarkers
  • Blood Proteins