Efficacy of photobiomodulation therapy in mitigating skin radiation damage

Abstract

Background: The use of sophisticated radiation dose delivery and fractionation has significantly improved cancer care. One of these involves localized, sustained ionizing dose delivery termed brachytherapy. Despite it therapeutic efficacy, specific side effects of brachytherapy include localized skin damage and breakdown for which only palliative treatments are currently available. The use of low dose biophotonics treatments to promote tissue healing is termed photobiomodulation (PBM) therapy. The aim of this study was to evaluate efficacy and molecular pathways of PBM therapy using two common wavelengths, red and near-infrared (NIR) to treat radiation wounds in athymic mice subjected to brachytherapy (sustained ionizing radiation from 125I seeds). Study Design/Materials and Method: A pilot study was performed with thirty-six athymic mice were accomplished for 60 days and divided into six groups: Surgical Control Group (No radiation and no PBM treatments); Radiation Control Group (125I seed 0.4252 mCi, no PBM); NIR-PBM Control Group (NIR PBM alone, LED at l¼880 nm); Red-PBM Control Group (Red PBM alone LED at l¼660 nm); Radiation- NIR PBM Group; Radiation-Red PBM Group. Following 21 days, radiation-induced wounds are evident. PBM treatments (both wavelengths with output power 40mW for 20 s, fluence 20 J/cm2 on top of implantation site) were performed every week up to 60 days. Wounds were evaluated every 7 days digital imaging, Laser Doppler Flowmetry (LDF) and tissue temperature with a thermographic camera. We also performed mPET-CT imaging using radioactive fluorodeoxyglucose (18F-FDG) at 51 and 81 days post-implantation. Animals were sacrifices progressively at each time point to correlate clinical observations with imaging and molecular tissue analyses. Tissues were collected to analyze molecular pathways correlating with inflammation, immune response, wound healing and angiogenesis using mRNA (qRT-PCR) and protein expression (immunostaining). Results: Both PBM treated groups demonstrated significant (p<0.05) improvements in skin radiation wound healing as compared to radiation group. Distinct improvements in clinical wound size and closure, improved tissue perfusion and reduced inflammation as evidenced by decreased wound thermal images. These wounds were also noted to have significant differences in the cytokine profiles (TGF-b, VEGF and PDGF) correlating with better healing responses. Radiation damage reduces brown fat composition that can potentially contribute to additional radiation-associated morbidities. The mPET-CT imaging noted significant preservation of brown fat composition in PBM-treated radiation alone groups. Further validation of these pathways is ongoing. Conclusion: Within the parameters of this study, PBM treatments demonstrated improved healing in radiation wounds due to ionizing radiation from 125I seeds. Ongoing work is examining the precise molecular pathways contributing to these therapeutic benefits. It is hoped this study will enable further development of this innovative therapy for managing side- effects from radiation treatments.