Expanded Characterization of a Hemi-Body Shielded Göttingen Minipig Model of Radiation-induced Gastrointestinal Injury Incorporating Oral Dosing Procedures.

In collaboration with the Biomedical Advanced Research and Development Authority (BARDA), the authors recently conducted a pilot study in a hemi-body shielded model of radiation-induced gastrointestinal (GI) injury in Göttingen minipigs following exposure to radiation dose levels between 8-16 Gy. Herein, the impact of oral dosing procedures is assessed, as well as the specific causes of death in animals exposed to radiation doses of 14 and 16 Gy (n = 64; 32 male, 32 female, between 6 and 8 mo of age). Oral dosing using a 2-tablet placebo system comprised of both immediate release and enteric-coated tablets starting 24 h post-irradiation resulted in inhibited gastric emptying of the enteric-coated tablets, which were found to be retained in the stomach and/or regurgitated. This finding appears to be species-specific, as similar findings have not been reported for other large animal species (e.g., non-human primates). Mortality was primarily dictated by decreased activity, body weight loss (>35%), and/or respiratory distress, despite shielding of the lung. The cause of respiratory distress in animals that were pre-terminally euthanized varied according to the timing of death, with interstitial inflammation and extensive fibrosis observed >20 days post-irradiation. Kidney damage was also identified in most animals after day 10. Changes in the GI tract were consistent with previous studies and included collagen deposition/fibrosis. Observations of inflammatory infiltrates and interstitial inflammation/fibrosis in both shielded and unshielded organs support a strong secondary inflammatory syndrome post-irradiation.