Photodynamic therapy with topical methyl‐ and hexylaminolevulinate for prophylaxis and treatment of UV‐induced SCC in hairless mice

Please cite this paper as: Photodynamic therapy with topical methyl‐ and hexylaminolevulinate for prophylaxis and treatment of UV‐induced SCC in hairless mice. Experimental Dermatology 2010; 19 : e166–e172. Abstract Background: Hexyl aminolevulinate (HAL) is a long‐chained 5‐aminolevulinic acid‐ester that has been proposed as a novel photosensitizing agent to methyl aminolevulinate (MAL) in topical photodynamic therapy (PDT). The more lipophilic HAL, may improve treatment outcome for non‐melanoma skin cancer. Objective: To compare the prophylactic and therapeutic effects of HAL‐ and MAL‐PDT for ultraviolet‐induced squamous cell carcinomas (SCCs) in hairless mice. Methods: Mice (n = 249) were irradiated with solar UV‐radiation (UVR) until SCC occurred. Before any skin changes developed, two prophylactic PDT treatments were given, using creams of HAL (2%, 6%, 20%) or MAL (20%) followed by illumination (632 nm, Aktilite, Photocure). Two therapeutic PDT‐treatments were given by randomization to the first developed SCC of 1 mm. Primary end‐points were time to first SCC of 1 mm and complete SCC clearance. Secondary end‐points were time to SCC‐recurrence, PpIX fluorescence and skin reactions to PDT. Results: The median time to first SCC was significantly longer for mice treated with prophylactic HAL‐PDT (2%, 6% and 20% HAL, 264 days) and MAL‐PDT (20% MAL, 269 days) than mice exposed to UVR (186 days) and UVR + placebo‐PDT (199 days) (P < 0.0001). The therapeutic efficacy of HAL‐ and MAL‐PDT showed cure rates of 23–61.5% (P = 0.11). Similar PpIX fluorescence intensity and severity of clinical reactions were seen for HAL‐ and MAL‐groups, although mice developed more intense hyper‐pigmentation when treated with 20% MAL‐PDT compared with 2% HAL‐PDT. Conclusions: PDT with HAL (2%, 6% and 20%) and MAL (20%) is equally effective to prevent and treat UV‐induced SCC in hairless mice.