Focused radiation exposure to the thorax region results in a characteristic dose- and time-dependent sequelae of lung disease characterized by the development of pneumonitis progressing to pulmonary fibrosis. 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 profile for WTLI specific to this institution, an endeavor necessary to validate the model prior to conducting efficacy studies under the criteria of the FDA 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, 25% at 10 Gy, 62.5% at 10.5 Gy, 87.5% at 11 Gy e, and 100% at 11.5 Gy. The resulting probit plot for the WTLI model estimated a 180-day LD50 of 10.28 Gy, which compares well with the previously published estimate of 10.27 Gy for the male rhesus. Microscopic findings included appearance of fibroplasia of the interstitium, edema of the alveoli, hyperplasia of the bronchiolar epithelium, and hyperplasia of type II pneumonocytes. Additionally, microscopic findings for unscheduled euthanasia included dose related observations of myocardial degeneration of the heart which contributed to moribundity. 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. Therefore, lung fibrosis can be reproducibly developed in this large animal model.
K.D. Thrall¹, S. Mahendra², V. Bunker¹, T. Rogers¹ ¹SNBL USA, Everett WA; ²Northwest Medical Physics Center, Lynnwood, WA,