Porphyrin biodistribution in UV-exposed murine skin after methyl- and hexyl-aminolevulinate incubation.
Topical photodynamic therapy (PDT) with methyl-aminolevulinate (MAL) is a well-established treatment for precancerous skin lesions and non-melanoma skin cancer. Treatment outcomes are less effective for thick than for superficial lesions, which are presumed to be due to insufficient PpIX biodistribution in tumour tissue. Hexyl-aminolevulinate (HAL) is a more lipophilic photosensitizer precursor than MAL and may penetrate the skin to a greater depth and more homogeneously. We compared HAL- and MAL-induced PpIX accumulation in specific skin compartments using concentrations of 2%, 6% and 20% HAL and MAL on long-term UV-irradiated mouse skin. Furthermore, 20% HAL and 20% MAL were applied to non-irradiated skin. Porphyrin fluorescence was measured by fluorescence microscopy in selected skin regions: the epidermis, superficial dermis, deep dermis and sebaceous gland epithelium down to a depth of 1 mm. We found higher PpIX fluorescence intensities in epidermis and sebaceous gland epithelium from 2%, 6% and 20% HAL (median 72-104 au) than in corresponding concentrations of MAL (median 35-69 au) (P < 0.01). Fluorescence intensities in the superficial (35 au) and deep dermis (32 au) were similar for HAL and MAL (P = 0.51) and lower than epidermal fluorescence intensities (P < 0.001). Significantly, higher median PpIX fluorescence intensities (64 au) were found in 20% MAL-incubated skin irradiated with UV than in non-irradiated skin (48 au) (P < 0.001). HAL-induced fluorescence intensities did not depend on UV exposure (HAL 20%, UV: 72 au, non-UV: 70 au) (P = 0.87). In conclusion, HAL express high affinity for epidermis and sebaceous gland epithelium, and MAL for actinically damaged skin, which raises future perspectives for improved selectivity in PDT.
Department of Dermatology, Bispebjerg Hospital, Copenhagen, Denmark. ktogsverdbo@dadlnet.dk
Katrine
K
Togsverd-Bo
Catharina M
CM
Lerche
Peter A
PA
Philipsen
Thomas
T
Poulsen
Hans Christian
HC
Wulf
Merete
M
Haedersdal
D000287:Administration, Topical; D000622:Aminolevulinic Acid / Q000008:administration & dosage / Q000031:analogs & derivatives / Q000493:pharmacokinetics; D000818:Animals; D001682:Biological Availability; D005260:Female; D006801:Humans; D051379:Mice; D008812:Mice, Hairless; D008856:Microscopy, Fluorescence; D023421:Models, Animal; D010778:Photochemotherapy; D017319:Photosensitizing Agents / Q000008:administration & dosage / Q000493:pharmacokinetics; D011166:Porphyrins / Q000378:metabolism*; D011230:Precancerous Conditions / Q000188:drug therapy; D011524:Protoporphyrins / Q000378:metabolism; D012867:Skin / Q000187:drug effects / Q000378:metabolism* / Q000528:radiation effects*; D012878:Skin Neoplasms / Q000188:drug therapy; D014018:Tissue Distribution; D014466:Ultraviolet Rays / Q000009:adverse effects*
D017319:Photosensitizing Agents; D011166:Porphyrins; D011524:Protoporphyrins; C475457:methyl 5-aminolevulinate; D000622:Aminolevulinic Acid; C028025:protoporphyrin IX; C419924:5-aminolevulinic acid hexyl ester