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

Katrine Togsverd-Bo, Catharina M Lerche, Thomas Poulsen, Hans Christian Wulf, Merete Haedersdal, Catharina M Lerche

25 Citationer (Scopus)

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.

OriginalsprogEngelsk
TidsskriftExperimental Dermatology
Vol/bind19
Udgave nummer8
Sider (fra-til)e166-72
ISSN0906-6705
DOI
StatusUdgivet - 1 aug. 2010

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