Characterization of Cutaneous Radiation Syndrome in a Mouse Model Using [18F]F- Fluorodeoxyglucose Positron Emission Tomography.

Abstract

Abstract: Ionizing radiation on the skin has the potential to cause various sequelae affecting quality of life and even leading to death due to multi-system failure. The development of radiation dermatitis is attributed to oxidative damage to the skin's basal layer and alterations in immune response, leading to inflammation. Past studies have shown that [18F]F-2-fluoro-2-deoxyglucose positron emission tomography-computed tomography ([18F]F-FDG PET/CT) can be used effectively for the detection of inflammatory activity, especially in conditions like hidradenitis suppurativa, psoriasis, and early atherosclerosis. Since currently there are no specific tests for radiation dermatitis, our study aimed to validate whether radiation dermatitis induced in mice can be accurately visualized and measured using [18F]F-FDG PET/CT. We induced cutaneous radiation syndrome in BALB/c mice with different radiation absorbed doses and monitored symptom development through photography, PET imaging, and histopathology, marking the first attempt at non-invasively quantifying radiation dermatitis effects at the molecular level using PET imaging. Our results showed that there were progressive changes in the dorsal skin of irradiated mice, with notable differences between those exposed to varying doses of radiation. Erythema, epilation, and desquamation were more pronounced in mice exposed to lower doses (25 Gy and 35 Gy) than at 45 Gy; however, by the third week, severe skin deterioration, including ulceration and dermal atrophy, was evident in mice irradiated with 35 Gy and 45 Gy. PET/CT imaging revealed increased [18F]F-FDG uptake in the irradiated dorsal skin area of all mice compared to controls, with more pronounced avidity for the lesion in the 25 Gy and 35 Gy than the 45 Gy. Comparison of tissue-normalized SUVMax values showed that both the 25 Gy and 35 Gy mice exhibited fourfold [18F]F-FDG uptake in the dorsal skin compared to controls, while a twofold uptake was seen at 45 Gy, thus indicating substantial metabolic changes in the dorsal skin induced by radiation exposure. Histopathological analyses correlated with the above findings, demonstrating generalized hypertrophy and epidermal thickening in all irradiated mice compared to controls, with thicker epidermis observed with higher radiation doses and increased destruction of microvasculature. In conclusion, PET/CT emerges as a successful tool for imaging cutaneous radiation syndrome, with the observed dermal changes in irradiated mice closely aligning with metabolic alterations of the affected area.