TY - JOUR
T1 - Porphyrin biodistribution in UV-exposed murine skin after methyl- and hexyl-aminolevulinate incubation
AU - Togsverd-Bo, Katrine
AU - Lerche, Catharina M
AU - Philipsen, Peter A
AU - Poulsen, Thomas
AU - Wulf, Hans Christian
AU - Haedersdal, Merete
N1 - © 2012 John Wiley & Sons A/S.
PY - 2012/4
Y1 - 2012/4
N2 - 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 1mm. We found higher PpIX fluorescence intensities in epidermis and sebaceous gland epithelium from 2%, 6% and 20% HAL (median 72-104au) than in corresponding concentrations of MAL (median 35-69au) (P<0.01). Fluorescence intensities in the superficial (35au) and deep dermis (32au) were similar for HAL and MAL (P=0.51) and lower than epidermal fluorescence intensities (P<0.001). Significantly, higher median PpIX fluorescence intensities (64au) were found in 20% MAL-incubated skin irradiated with UV than in non-irradiated skin (48au) (P<0.001). HAL-induced fluorescence intensities did not depend on UV exposure (HAL 20%, UV: 72au, non-UV: 70au) (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.
AB - 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 1mm. We found higher PpIX fluorescence intensities in epidermis and sebaceous gland epithelium from 2%, 6% and 20% HAL (median 72-104au) than in corresponding concentrations of MAL (median 35-69au) (P<0.01). Fluorescence intensities in the superficial (35au) and deep dermis (32au) were similar for HAL and MAL (P=0.51) and lower than epidermal fluorescence intensities (P<0.001). Significantly, higher median PpIX fluorescence intensities (64au) were found in 20% MAL-incubated skin irradiated with UV than in non-irradiated skin (48au) (P<0.001). HAL-induced fluorescence intensities did not depend on UV exposure (HAL 20%, UV: 72au, non-UV: 70au) (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.
U2 - 10.1111/j.1600-0625.2012.01442.x
DO - 10.1111/j.1600-0625.2012.01442.x
M3 - Journal article
C2 - 22320713
SN - 1600-0625
VL - 21
SP - 260
EP - 264
JO - Experimental Dermatology
JF - Experimental Dermatology
IS - 4
ER -
