Artificial daylight photodynamic therapy with "non-inflammatory" doses of hexyl aminolevulinate only marginally delays SCC development in UV-exposed hairless mice.
Photodynamic therapy (PDT) is effective for actinic keratoses, but is associated with pain and post-treatment inflammation. Daylight-mediated PDT and PpIX-precursors at low concentrations reduce pain and inflammation intensity. The objective was to evaluate the effect of repeated low-concentration PDT combined with artificial daylight on SCC development. Mice (n = 265) were exposed to simulated solar UV-irradiation (UVR) 3 times weekly mimicking "summer-dose"-exposure (3 SED). Selected groups of mice received a "winter-dose"-exposure (0.6 SED) for the first 90 days. PDT was delivered with 0.1%, 0.05% and 0.02% hexyl aminolevulinate (HAL) cream and artificial daylight for 2.5 hours (6 J cm(-2)) in different treatment regimes (1-3 times weekly, 45-days intervals, days 1-180 and from day 180 onwards). The primary end-point was the time to first SCC (1 mm diameter). 0.1% HAL-PDT given 3 times weekly slightly delayed SCC development and induced minimal inflammation. In winter- and summer UVR-treatment regimes, 0.1% HAL PDT delayed the time to first SCC compared to control UVR and placebo-PDT when mice were PDT-treated on days 1-180 (median 213 vs. 199 days, p = 0.011) and from day 180 onwards (median 218 vs. 199 days, p = 0.006). PDT with 0.05% and 0.02% HAL did not influence SCC development (medians 206 days, p = ns). In summer UVR-exposed mice, 0.1% HAL-PDT marginally postponed the time to first SCC compared to control UVR (median 160 days) when treatments were given 3 times weekly for 180 days (median 166, p = 0.01), but not for 90 days (median 161, p = 0.112). In conclusion, repeated low-concentration HAL-PDT combined with artificial daylight is well-tolerated, but only marginally delays SCC development in mice.
Department of Dermatology, Bispebjerg Hospital, Copenhagen, Denmark. ktogsverdbo@dadlnet.dk.
Katrine
K
Togsverd-Bo
Catharina M
CM
Lerche
Peter A
PA
Philipsen
Merete
M
Hædersdal
Hans Christian
HC
Wulf
D000622:Aminolevulinic Acid / Q000627:therapeutic use*; D000818:Animals; D002294:Carcinoma, Squamous Cell / Q000209:etiology / Q000517:prevention & control*; D005260:Female; D051379:Mice; D008812:Mice, Hairless; D010778:Photochemotherapy; D017319:Photosensitizing Agents / Q000627:therapeutic use*; D010858:Pigmentation / Q000528:radiation effects; D012878:Skin Neoplasms / Q000209:etiology / Q000517:prevention & control*; D013472:Sunlight; D014466:Ultraviolet Rays
D017319:Photosensitizing Agents; D000622:Aminolevulinic Acid