Dosimetry Characterization and Early-Phase Dose and Injury-Severity Biomarkers in a Rhesus Macaque Dose-Response Model System

The purpose of this study was to characterize radiation dosimetry and validate early-phase radiation biomarkers using a Rhesus macaque (Macaca mulatta) non-human-primate radiation model. Non-human-primates in pairs (male and females; 4.4 to 7.8 kg; 3.6 to 5.9 y) were exposed bilaterally to ⁶⁰Co-gamma rays to midline doses of 0, 1, 3.5, 6.5 and 8.5 Gy at ~0.55 Gy/min (n = 6/dose). The exposure intervals were determined based on dose-rate measurements using cylindrical water phantoms with the alanine – electron paramagnetic resonance system traceable to the National Institute of Standards and Technology. Field uniformity was characterized and the physics reference doses were measured at the mid-line at the height of the xiphoid process. Blood was sampled for measurements of hematology and blood chemistry radio-responses prior to irradiation and up to 4 d after exposure. The field in the area occupied by the animals was uniform within approximately ± 0.5% in the lateral direction, within approximately ± 1.5% in the anterior-posterior direction, and within approximately ± 2% in the superior-inferior direction. Exposure to 1, 3.5, 6.5, and 8.5 Gy causes a dramatic increase in amylase activity (~1.9, ~3.1, ~8.3, ~13.3 fold, respectively) at 1 d after exposure (p= <0.001) along with more than 60, 80, and 90% depletion of lymphocyte at 1, 3.5, and higher doses 6.5 or 8.5 Gy, respectively. Hematological (i.e., lymphocyte depletion and increases in neutrophil to lymphocyte ratios at 1-3 d) and blood chemistry (i.e., serum amylase activity at 1 d) radiation biomarkers demonstrate useful diagnostic utility for life-threatening radiation exposure assessment.