The Gastrointestinal Subsyndrome of the Acute Radiation Syndrome in Rhesus Macaques: A Systematic Review of the Lethal Dose-response Relationship With and Without Medical Management

Well-characterized animal models that mimic the human response to potentially lethal doses of radiation are required to assess the efficacy of medical countermeasures under the criteria of the US Food and Drug Administration's Animal Rule. Development of a model for the gastrointestinal acute radiation syndrome requires knowledge of the radiation dose-response relationship and time course of mortality and morbidity across the acute and prolonged gastrointestinal radiation syndrome. The nonhuman primate, rhesus macaque, is a relevant animal model that has been used to determine the efficacy of medical countermeasures to mitigate major signs of morbidity and mortality relative to the hematopoietic acute radiation syndrome, gastrointestinal acute radiation syndrome, and lung injury. It can be used to assess the natural history of gastrointestinal damage, concurrent multiple organ injury, and aspects of the mechanism of action for acute radiation exposure and treatment. A systematic review of relevant studies that determined the dose-response relationship for the gastrointestinal acute and prolonged radiation syndrome in the rhesus macaque relative to radiation dose, quality, dose rate, exposure uniformity, and use of medical management has never been performed.