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Abstract
Purpose: To develop mitigators for combined irradiation to the lung and skin.
Methods: Rats were treated with X-rays as follows: (1) 12.5 or 13 Gy whole thorax irradiation (WTI); (2) 30 Gy soft X-rays to 10% area of the skin only; (3) 12.5 or 13 Gy WTI + 30 Gy skin irradiation after 3 hours; (4) 12.5 Gy WTI + skin irradiation and treated with captopril (160 mg/m2/day) started after 7 days. Our end points were survival (primary) based on IACUC euthanization criteria and secondary measurements of breathing intervals and skin injury. Lung collagen at 210 days was measured in rats surviving 13 Gy WTI.
Results: After 12.5 Gy WTI with or without skin irradiation, one rat (12.5 Gy WTI) was euthanized. Survival was less than 10% in rats receiving 13 Gy WTI, but was enhanced when combined with skin irradiation (p < 0.0001). Collagen content was increased at 210 days after 13 Gy WTI vs. 13 Gy WTI + 30 Gy skin irradiation (p < 0.05). Captopril improved radiation-dermatitis after 12.5 Gy WTI + 30 Gy skin irradiation (p = 0.008).
Conclusions: Radiation to the skin given 3 h after WTI mitigated morbidity during pneumonitis in rats. Captopril enhanced the rate of healing of radiation-dermatitis after combined irradiations to the thorax and skin.
Acknowledgements
This work honors Dr Michael Robbins who was an external advisor for the Rochester U-19 award which reviewed and funded the pilot project that initiated our study. Dr Robbins also contributed to reviewing the progress of this work. We thank Marylou Mäder for irradiating the rats and for the excellent care of these animals. This work was funded by NIH/NIAID agreements U19-AI091036 (Rochester) and 67734 (MCW), U01-AI107305 and RC1 AI81294 and 01S1 (BARDA).
Declaration of interest
The authors report no conflicts of interest. The authors alone are responsible for the content and writing of the paper.