title: Photobleaching during and re-appearance after photodynamic therapy of topical ALA-induced fluorescence in UVB-treated mouse skin.
abstract: Photodynamic therapy (PDT) using protoporphyrin IX (PpIX) induced by topically applied 5-aminolevulinic acid (ALA) seems a promising alternative for the treatment of superficial non-melanoma skin cancer and actinic keratosis. In this study, the kinetics of new PpIX fluorescence arising after a PDT treatment that had photobleached the original fluorescence were determined. Our purpose was to examine the feasibility of multiple irradiations, following a single topical ALA application, to increase PDT efficacy. In addition, photobleaching during PDT and the fluorescence spectra during and after PDT were studied. As a model we used hairless mice with and without UVB-induced skin lesions. ALA was applied to the skin for 4 hr. An illumination was delivered either immediately after application or 6 hr after the end of the application (at interval of maximum fluorescence). During PDT, the fluorescence of normal skin decreased at a faster rate than the fluorescence of the skin lesions. In the fluorescence study after PDT, the areas treated immediately post-application showed a fluorescence increase over time similar to that in non-treated areas on the same mice. A remarkable result was that the fluorescence of areas treated at maximum fluorescence increased, whereas the fluorescence of non-treated areas did not increase over time. With both treatment intervals the new fluorescence showed a characteristic PpIX spectrum. Our results demonstrate that a second illumination, when new PpIX fluorescence has been formed, may increase PDT efficacy after topical ALA application. This finding has been demonstrated previously for systemic ALA administration.
authors.affiliation: Department of Clinical Physics, Dr. Daniel den Hoed Cancer Centre, Rotterdam, The Netherlands.
authors.forename: N
authors.initials: N
authors.lastname: Van der Veen
authors.forename: H S
authors.initials: HS
authors.lastname: De Bruijn
authors.forename: W M
authors.initials: WM
authors.lastname: Star
mesh_terms: D000287:Administration, Topical; D000622:Aminolevulinic Acid / Q000008:administration & dosage / Q000494:pharmacology*; D000818:Animals; D005260:Female; D051379:Mice; D008815:Mice, Inbred Strains; D010777:Photochemistry; D010778:Photochemotherapy; D017319:Photosensitizing Agents / Q000494:pharmacology*; D011355:Prodrugs / Q000008:administration & dosage / Q000494:pharmacology*; D011524:Protoporphyrins / Q000494:pharmacology*; D011833:Radiation Injuries, Experimental / Q000628:therapy*; D012867:Skin / Q000293:injuries* / Q000528:radiation effects; D014466:Ultraviolet Rays
chemical_list: D017319:Photosensitizing Agents; D011355:Prodrugs; D011524:Protoporphyrins; D000622:Aminolevulinic Acid; C028025:protoporphyrin IX