Photodynamic therapy with topical methyl- and hexylaminolevulinate for prophylaxis and treatment of UV-induced SCC in hairless mice.
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.
Togsverd-Bo
Katrine
K
Department of Dermatology, Bispebjerg Hospital, Copenhagen, Denmark. katrinetogsverd@hotmail.com
Lerche
Catharina M
CM
Poulsen
Thomas
T
Wulf
Hans Christian
HC
Haedersdal
Merete
M
D000287:Administration, Topical; D000622:Aminolevulinic Acid / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000627:therapeutic use; D000818:Animals; D002294:Carcinoma, Squamous Cell / Q000188:drug therapy* / Q000209:etiology / Q000517:prevention & control; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D005260:Female; D051379:Mice; D008812:Mice, Hairless; D009381:Neoplasms, Radiation-Induced / Q000188:drug therapy* / Q000517:prevention & control; D010778:Photochemotherapy / Q000379:methods*; D017319:Photosensitizing Agents / Q000008:administration & dosage / Q000627:therapeutic use; D012878:Skin Neoplasms / Q000188:drug therapy* / Q000209:etiology / Q000517:prevention & control; D016896:Treatment Outcome; D014466:Ultraviolet Rays / Q000009:adverse effects*
D017319:Photosensitizing Agents; C475457:methyl 5-aminolevulinate; D000622:Aminolevulinic Acid; C419924:5-aminolevulinic acid hexyl ester