Porphyrin biodistribution in UV-exposed murine skin after methyl- and hexyl-aminolevulinate incubation

Exp Dermatol. 2012 Apr;21(4):260-4. doi: 10.1111/j.1600-0625.2012.01442.x. Epub 2012 Feb 10.


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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Administration, Topical
  • Aminolevulinic Acid / administration & dosage
  • Aminolevulinic Acid / analogs & derivatives
  • Aminolevulinic Acid / pharmacokinetics
  • Animals
  • Biological Availability
  • Female
  • Humans
  • Mice
  • Mice, Hairless
  • Microscopy, Fluorescence
  • Models, Animal
  • Photochemotherapy
  • Photosensitizing Agents / administration & dosage
  • Photosensitizing Agents / pharmacokinetics
  • Porphyrins / metabolism*
  • Precancerous Conditions / drug therapy
  • Protoporphyrins / metabolism
  • Skin / drug effects
  • Skin / metabolism*
  • Skin / radiation effects*
  • Skin Neoplasms / drug therapy
  • Tissue Distribution
  • Ultraviolet Rays / adverse effects*


  • Photosensitizing Agents
  • Porphyrins
  • Protoporphyrins
  • methyl 5-aminolevulinate
  • Aminolevulinic Acid
  • protoporphyrin IX
  • 5-aminolevulinic acid hexyl ester