Abstract
Despite significant radiobiological advancements following World War II, only a limited number of medical countermeasures (MCMs) have been approved by the United States Food and Drug Administration (US FDA) for acute radiation exposure related illnesses. Accordingly, well-characterized and validated animal models, both large and small, are still very much needed to develop safe and effective countermeasures. Animal models that are used for such purposes need to reflect not only the clinical and pathogenic features of those seen in radiation exposed humans, but also comparable radiation dose- and time-dependent relationships. The objective of the present study therefore was to further characterize the response patterns of rhesus nonhuman primates exposed to total-body, potentially lethal, radiation doses using the Armed Forces Radiobiology Research Institute high level cobalt-60 gamma-radiation source. Response patterns of male and female rhesus macaques were assessed following acute, total-body exposures to potentially lethal, gamma rays (5.8, 6.5, and 7.2 Gy). Groups of 15, 16, and 8 animals were exposed to the three radiation doses, respectively. All animals were provided a minimum, subject-based supportive care, that excluded the use of blood products. Blood products were excluded in order to replicate a large scale radiological/nuclear scenario treatment option in which access to blood products may be limited or unavailable. This is also relevant for military scenarios, in which medical facilities may not have the appropriate capabilities for blood transfusions. All animals were clinically monitored for 60 days post-irradiation. Survival was the primary endpoint of this study, while secondary endpoints included recovery of various hematopoietic elements. The mortality rates of the rhesus macaques were 33%, 37.5% and 50%, respectively, for the three radiation doses (i.e., 5.8, 6.5 and 7.2 Gy). Within the surviving animals, hematological blood values had returned largely to pre-exposure levels by the end of the study period. The results of this study provides foundational data on the use of the rhesus macaque model for subsequent development and testing of new radiation MCMs, as per required by the US FDA Animal Rule.