Comparison of sensitivity of rhesus and cynomolgus macaque for acute radiation effects.

Radiation medical countermeasure development under the United States Food and Drug Administration Animal Rule needs validated large animal models of acute radiation syndrome. Such a well-established large animal model is the rhesus nonhuman primate. The potential use of the rhesus for other high priority areas and limited supply of such animals emphasizes the need to validate other large animal models, in particular other macaque models, in order to compensate for the lack of rhesus macaques for radiation countermeasure development. Based on existing data, cynomolgus macaques, Macaca fascicularis, are a viable alternative, but need further characterization. Reliance on such animal models requires that the models are well validated. Data gathered from rhesus and cynomolgus macaques under the same experimental conditions are not available; therefore, the authors compared and contrasted here the radiosensitivity of both macaques receiving same levels of clinical support and exposed to same doses of total-body gamma-radiation, and at same dose rates using same radiation source. Under matched experimental conditions, significant differences between acutely irradiated rhesus and cynomolgus macaques relative to the rates of survival and blood cell changes were observed. The presented data demonstrate that the cynomolgus macaque is more sensitive to ionizing radiation exposure. Overall, data supports the concept that the cynomolgus macaque is a viable, potentially useful alternative large animal model for the evaluation of radiation medical countermeasures. For comparative purposes however, additional studies with both macaques under identical experimental conditions, such as levels of clinical support and different radiation qualities with males and females ran concurrently in future will be critically important.