Radiation Medical Countermeasures and Use of EPR Biodosimetry to Facilitate Effectiveness of Applied Clinical Procedures

Abstract

The utility for electron paramagentic resonance (EPR or ESR)-based radiation biodosimetry has received increasing recognition concerning its potential to assist in guiding the clinical management of medical countermeasures in individuals unwantedly exposed to injurious levels of ionizing radiation. Similar to any of the standard physical dosimetric methods currently employed for screening clinically significant radiation exposures, the EPR-based in vivo dosimetry approach would serve to complement and extend clinical assessments (e.g., blood analyses, cytogenetics, etc.), specifically to more accurately assign the extent of ionizing radiation exposure that individuals might have received. In the case of EPR biodosimetry of biological samples such as nails, teeth, and bones, the method has the capability of providing information on the physical dose at several specific bodily sites and perhaps additonal information on the homogeneity of the exposure as well as its overall magnitude. This information on radiation dose and distribution would be of significant value in providing medical management to given individuals at health risk due to radiation exposure. As these measurements provide information solely on physical measures of the radiation dose and not on the potential biological impact of a particular dose, they are complementary, albeit supplemental, to the array of currently available biologically based biodosimetry and clinical findings. In aggregate, these physical and biological measures of radiation exposure levels (dose) would most certainly provide additional, useful information for the effective medical management of radiation exposed individuals.

Effects of combined ciprofloxacin and Neulasta therapy on intestinal pathology and gut microbiota after high-dose irradiation in mice

“…GI-ARS usually follows radiation exposure at a higher dose than H-ARS; thus, there could be an interplay of myelosuppression and GI injury. There is adequate evidence on the efficacy of FDA-approved growth factors mitigating the effects of H-ARS and improving survival in a variety of animal models ( 12 , 15 , 17 , 38 , 39 ). Recently, the effect of these FDA-approved treatments on the incidence and severity of GI-ARS was investigated using this mouse model consisting of 9.5 Gy 60 Co γ-photon total body radiation.…”

“…However, limitations include the impact that cancer itself has on the gut microbiota ( 11 ). In humans, GI-ARS leads to mortality 2–3 weeks post-radiation exposure ( 12 ). A mass casualty nuclear event would require a substantial public health effort including the use of the Strategic National Stockpile (SNS) that has been established to immediately distribute medical countermeasures (MCMs) and supplies.…”

“…Small and large animal models are invaluable in the development of MCMs, testing of drug combinations, and understanding the mechanisms of radiation injury at higher doses ( 18 ). To this end, no FDA-approved MCMs exist for the treatment of GI-ARS and the impact of H-ARS therapies on GI symptoms induced by higher radiation doses is lacking ( 12 ).…”