Protein biomarkers for enhancement of radiation dose and injury assessment in nonhuman primate total-body irradiation model

Abstract

Development and validation of early-response radiation injury biomarkers are critical for effective triage and medical management of irradiated individuals. Plasma protein and haematological profiles were evaluated using multivariate linear-regression analysis to provide dose-response calibration curves for photon-radiation dose assessment in 30 rhesus macaques total-body-irradiated to 1-8.5 Gy with (60)Co gamma rays (0.55 Gy min(-1)). Equations for radiation dose received were established based on different combinations of protein biomarkers [i.e. C-reactive protein (CRP), serum amyloid A (SAA), interleukin 6 (IL-6) and Flt3 Ligand (Flt3L)] at samples collection time-points 6 h, 1, 2, 3, 4 and 7 d post-total-body irradiation. Dynamic changes in the levels of CRP, SAA, IL-6 and Flt3L may function as prognostic indicators of the time course and severity of acute radiation sickness (ARS). The combination of protein biomarkers provides greater accuracy for early radiation assessment than any one biomarker alone.

Detection of Acute Radiation Sickness: A Feasibility Study in Non-Human Primates Circulating miRNAs for Triage in Radiological Events

“…Gastrointestinal effects are prominent at doses greater than 5–6 Gy and progress more rapidly, while neurovascular collapse ensues at doses greater than 10–20 Gy which occurs immediately [2,3]. Rapid and early diagnosis is essential as demonstrated by the dramatic increase in survival rates if treatments are administered within few days after exposure [4,5]. …”

Identifying Urinary and Serum Exosome Biomarkers for Radiation Exposure Using a Data Dependent Acquisition and SWATH-MS Combined Workflow

“…Elevation of several acute phase proteins in WBI mice indicated rapid systemic inflammatory response possibly due to damage of vascular endothelial cells. Interestingly, some cytokines (IL6) and acute response proteins (CRP) reported to show radiation-responsive profile [27] were not identified in our serum exosomes analysis suggesting that exosome analysis can be restrictive and may miss important cues otherwise detectable in whole serum analysis.…”

State-of-the-Art Advances in Radiation Biodosimetry for Mass Casualty Events Involving Radiation Exposure

“…Expression profiles of several individual protein biomarkers have been examined for their relationship to received radiation dose and exposure pattern. In a TBI nonhuman primate (NHP) model, dose-dependent increases in CRP, SAA, FIT3 Ligand (FL), Interleukin-6 (IL6) and amylase were observed in the peripheral blood ( 28 – 30 ). Similar changes in expression were seen in plasma for SAA, FL, IL6 and G-CSF in TBI mice models ( 31 – 33 ).…”

“…Compared to traditional cytogenetic techniques, hematological markers are faster and utilize existing high-throughput methodologies. In several studies, it has been reported that a combined approach using analysis of blood cell populations with concurrent measurement of serum-soluble protein biomarkers shows a strong correlation between predicated and actual received dose in mouse and NHP models (28, 29, 31, 33, 91). In addition, successful use of a multivariate approach in the clinical management of victims of the Dakar radiation accident was reported, in which 63 individuals were screened to determine the level of radiation exposure using a combination of classic cytogenetic biodosimetry, evaluation of blood cell population and measurement of FL.…”