Non-human Primate Total-body Irradiation Model with Limited and Full Medical Supportive Care Including Filgrastim for Biodosimetry and Injury Assessment

Radiat Prot Dosimetry. 2016 Dec;172(1-3):174-191. doi: 10.1093/rpd/ncw176. Epub 2016 Jul 29.

Abstract

An assessment of multiple biomarkers from radiation casualties undergoing limited- or full-supportive care including treatment with filgrastim is critical to develop rapid and effective diagnostic triage strategies. The efficacy of filgrastim with full-supportive care was compared with results with limited-supportive care by analyzing survival, necropsy, histopathology and serial blood samples for hematological, serum chemistry and protein profiles in a non-human primate (Macaca mulatta, male and female) model during 60-d post-monitoring period following sham- and total-body irradiation with 6.5 Gy 60Co gamma-rays at 0.6 Gy min-1 Filgrastim (10 μg kg-1) was administered beginning on Day 1 post-exposure and continued daily until neutrophil counts were ≥2,000 μL-1 for two consecutive days. Filgrastim and full-supportive care significantly decreased the pancytopenia duration and resulted in improved animal survival and recovery compared to animals with a limited-supportive care. These findings also identified and validated a multiparametric biomarker panel to support radiation diagnostic device development.

MeSH terms

  • Animals
  • Biological Assay / methods*
  • Biomarkers / blood
  • Disease Models, Animal*
  • Female
  • Filgrastim / therapeutic use*
  • Macaca mulatta
  • Male
  • Radiation Dosage
  • Radiation Exposure / analysis
  • Radiation Injuries / blood
  • Radiation Injuries / diagnosis*
  • Radiation Injuries / therapy*
  • Radiation Monitoring / methods*
  • Radiation-Protective Agents / therapeutic use
  • Reproducibility of Results
  • Sensitivity and Specificity
  • Treatment Outcome
  • Whole-Body Irradiation / methods*

Substances

  • Biomarkers
  • Radiation-Protective Agents
  • Filgrastim