Single preventative ALA-PDT treatment reduces carcinogenesis in a mouse model of photocarcinogenesis

Summary: Abstract Body: Delta-aminolevulinic acid (ALA) photodynamic therapy (PDT) is widely used to treat actinic keratoses and early non-melanoma skin cancer, but its effects on skin cancer prevention are under-studied. ALA incubation times and light delivery vary widely in clinical practice, making it crucial to identify the optimal duration that maximizes therapeutic efficacy and consistency. This study evaluated the optimal ALA incubation time in the SKH1 mouse model and its impact on tumor formation when used preventatively. Mice were incubated with 10% nanoemulsion ALA gel for 0.5,1, and 3 hrs (n=3 per group), followed by red-light PDT (630nm, 37J/cm2). Protoporphyrin-IX (PpIX) fluorescence was measured in each cohort using a blue light microscope (405nm), and acute PDT response was documented. Although PpIX fluorescence was highest after 3 hours of incubation, the acute response and subacute scabbing were well beyond the accepted human treatment response, thus, in SKH1 mice, 1 hour was the best incubation time to mimic human PDT treatment. To test the effect of a single preventative PDT treatment on the ability to reduce skin tumor formation in SKH1 mice treated for 10 weeks with solar-simulated light treatment (90mJ/cm2, UVB/UVA=0.048), we treated groups of mice (n=3) with 1-hour incubation ALA-PDT before any visible signs of carcinogenesis and followed tumor development for 12 weeks. PDT-treated areas had a significant 2.2-fold reduction (p=0.0037, one-way ANOVA and post-hoc Tukey testing) of tumors at 12 weeks after PDT compared to untreated controls in the treatment areas. This study presents critical data on PpIX conversion kinetics in SKH1 mice for using the model in PDT efficacy and combination treatment studies. Moreover, we also show the ability of optimally dosed PDT to prevent tumor development even when used well before the first visible signs of photocarcinogenesis. Rhea C. Rodrigues¹, Christopher M. Lawson², Erin C. Tracy¹, Sean P. Murphy¹, Ruby Acquah¹, S Bozsanyi¹, Gal Shafirstein², Wendy J. Huss¹, Gyorgy Paragh¹ 1. Dept. of Dermatology & Cell Stress Biology, Roswell Park Comprehensive Cancer Center, Buffalo, NY, United States. 2. PDT Center & Dept. of Cell Stress Biology, Roswell Park Comprehensive Cancer Center, Buffalo, NY, United States. UV Biology/Injury and Non-melanoma Cancers