The radiation dose response relationship for whole thorax lung irradiation in the female rhesus macaque
Karla D. Thrall,1, Saikanth Mahendra,2 Thomas J MacVittie3
1SNBL USA, Ltd., Everett, WA; 2Northwest Medical Physics Center, Lynnwood, WA; 3Department Of Radiation Oncology, University of Maryland, School of Medicine, Baltimore, MD
Radiation Research Society (RRS) Annual Meeting, Cancun, Mexico (2017).
Concerns over nuclear and radiological threats have prompted the need to improve methods to protect the general population from the health hazards associated with exposure to ionizing radiation. The development of effective medical countermeasures requires efficacy studies be conducted in an appropriate animal model (“the Animal Rule” 21 CFR 314.600 for drugs). However, the reliance on non-human efficacy data places an enormous importance on appropriately developed and validated animal models. A whole thorax lung irradiation (WTLI) model has been developed for the male rhesus macaque (Garofalo et al. 2014). The objective of this study was to develop a lethality dose response profile for WTLI specific to this institution, an endeavor necessary to validate the model prior to conducting efficacy studies under the criteria of the Animal Rule. The study design was similar to that described previously, with the exception that female, rather than male, rhesus macaques were utilized. In brief, a computed tomography (CT) scan was conducted prior to irradiation and used for treatment planning. Animals were exposed to a single 6 MV photon exposure focused to the lung as determined by the CT scan and treatment planning at a dose of 9.5, 10, 10.5, 11 or 11.5 Gy. Supportive care, including administration of dexamethasone, was based on trigger-to-treat criteria and clearly defined euthanasia criteria were used to determine moribund condition over 180 days post irradiation. Percent mortality per radiation dose was 12.5% at 9.5 Gy exposure, 25% at 10 Gy exposure, 62.5% at 10.5 Gy exposure, 87.5% at 11 Gy exposure, and 100% at 11.5 Gy exposure. The resulting probit plot for the WTLI model estimated a 180 day LD50 of 10.28 Gy, which compared well with the previously published estimate of 10.27 Gy for the male rhesus. Additionally, WTLI allows longitudinal definition of combined organ injury to both lung and heart. These data suggested the absence of a gender influence on the radiation dose response for WTLI in the rhesus and provided an inter-laboratory validation of the previously reported model.