Photodynamic therapy with topical methyl- and hexylaminolevulinate for prophylaxis and treatment of UV-induced SCC in hairless mice.

Abstract

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.

• Authors: Katrine Togsverd-Bo, Catharina M Lerche, Thomas Poulsen, Hans Christian Wulf, Merete Haedersdal
• Journal: Experimental dermatology (Exp Dermatol) Vol. 19 Issue 8 Pg. e166-72 (Aug 2010) ISSN: 1600-0625 [Electronic] Denmark
• PMID: 20100196 (Publication Type: Comparative Study, Journal Article)

Chemical References

• Photosensitizing Agents
• methyl 5-aminolevulinate
• Aminolevulinic Acid
• 5-aminolevulinic acid hexyl ester

Topics

• Administration, Topical
• Aminolevulinic Acid (administration & dosage, analogs & derivatives, therapeutic use)
• Animals
• Carcinoma, Squamous Cell (drug therapy, etiology, prevention & control)
• Disease Models, Animal
• Dose-Response Relationship, Drug
• Female
• Mice
• Mice, Hairless
• Neoplasms, Radiation-Induced (drug therapy, prevention & control)
• Photochemotherapy (methods)
• Photosensitizing Agents (administration & dosage, therapeutic use)
• Skin Neoplasms (drug therapy, etiology, prevention & control)
• Treatment Outcome
• Ultraviolet Rays (adverse effects)