Wise Stephen Y, Fatanmi Oluseyi O, Petrus Sarah A, Melendez-Miranda Issa, Brink Matthew, Packer Benjamin, Carpenter Alana D, Seed Thomas M, Singh Vijay K
Division of Radioprotectants, Department of Pharmacology and Molecular Therapeutics, F. Edward Hébert School of Medicine, Uniformed Services University of the Health Sciences, 4301 Jones Bridge Road, Bethesda, MD, 20814, USA.
Armed Forces Radiobiology Research Institute, Uniformed Services University of the Health Sciences, Bethesda, MD, 20814, USA.
Sci Rep. 2025 Aug 26;15(1):31378. doi: 10.1038/s41598-025-17099-7.
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.
尽管第二次世界大战后放射生物学取得了重大进展，但美国食品药品监督管理局（US FDA）仅批准了有限数量的针对急性辐射暴露相关疾病的医学应对措施（MCM）。因此，仍然非常需要特征明确且经过验证的大小动物模型，以开发安全有效的应对措施。用于此类目的的动物模型不仅需要反映辐射暴露人类所表现出的临床和致病特征，还需要反映可比的辐射剂量和时间依赖关系。因此，本研究的目的是使用武装部队放射生物学研究所的高剂量钴 - 60伽马辐射源，进一步表征恒河猴非人灵长类动物在全身接受潜在致死性辐射剂量后的反应模式。在雄性和雌性恒河猴急性全身暴露于潜在致死性伽马射线（5.8、6.5和7.2 Gy）后，评估其反应模式。分别有15只、16只和8只动物暴露于这三种辐射剂量。所有动物都接受了基于个体的最低限度支持性护理，其中不包括使用血液制品。不使用血液制品是为了模拟大规模放射/核情景下可能无法获得或难以获得血液制品的治疗选择。这对于军事情景也很重要，因为军事医疗设施可能没有输血的适当能力。所有动物在辐照后进行了60天的临床监测。生存是本研究的主要终点，而次要终点包括各种造血成分的恢复情况。三种辐射剂量（即5.8、6.5和7.2 Gy）下恒河猴的死亡率分别为33%、37.5%和50%。在存活的动物中，到研究期结束时，血液学血液值已基本恢复到暴露前水平。本研究结果为根据美国食品药品监督管理局动物规则要求将恒河猴模型用于后续新辐射MCM的开发和测试提供了基础数据。
