title: PpIX fluorescence kinetics and increased skin damage after intracutaneous injection of 5-aminolevulinic acid and repeated illumination.
abstract: Photodynamic therapy with topically applied 5-aminolevulinic acid is used successfully for superficial skin lesions. The results for thicker, nodular lesions are less favorable. The method of aminolevulinic acid administration, the concentrations of aminolevulinic acid, and the irradiation schemes used so far have not been investigated thoroughly. As aminolevulinic acid photodynamic therapy has high potential for the increasing problem of skin cancer, we investigated both visually and histopathologically the photodynamic-therapy-induced skin damage after intracutaneous administration of aminolevulinic acid in normal porcine skin. We also investigated the kinetics of the aminolevulinic-acid-induced photosensitizer protoporphyrin IX fluorescence after irradiation in relation to fluence and irradiance. Finally we investigated the effect on photodynamic-therapy-induced damage of a fractionated irradiation. This study demonstrates that intracutaneous administration of aminolevulinic acid leads to higher fluorescence levels and thus to formation of higher protoporphyrin IX concentrations than topical application of aminolevulinic acid cream. The peak level of protoporphyrin IX after intracutaneous administration of aminolevulinic acid is reached earlier than after topical administration. The comeback of fluorescence, indicating re-synthesis of protoporphyrin IX after irradiation, is inhibited with increasing fluence. Photodynamic-therapy-induced damage increases with increasing fluence, but is independent of the irradiance. Finally, the photodynamic-therapy-induced skin damage seems to be greater after fractionated irradiations with two equal light fractions of 15 J per cm2 separated by a dark interval of 2 h.
authors.affiliation: Department of Dermatology, University Hospital Maastricht, Maastricht, The Netherlands. mthis@sder.azm.nl
authors.forename: Monique R
authors.initials: MR
authors.lastname: Thissen
authors.forename: Mieke W
authors.initials: MW
authors.lastname: de Blois
authors.forename: Dominic J
authors.initials: DJ
authors.lastname: Robinson
authors.forename: Henriette S
authors.initials: HS
authors.lastname: de Bruijn
authors.forename: Richard P
authors.initials: RP
authors.lastname: Dutrieux
authors.forename: Willem M
authors.initials: WM
authors.lastname: Star
authors.forename: H A Martino
authors.initials: HA
authors.lastname: Neumann
mesh_terms: D000622:Aminolevulinic Acid / Q000008:administration & dosage* / Q000494:pharmacology; D000818:Animals; D004307:Dose-Response Relationship, Radiation; D005260:Female; D005453:Fluorescence; D007271:Injections, Intradermal; D007700:Kinetics; D008027:Light; D009994:Osmolar Concentration; D017319:Photosensitizing Agents / Q000008:administration & dosage* / Q000494:pharmacology; D011524:Protoporphyrins / Q000378:metabolism*; D019233:Retreatment; D012867:Skin / Q000187:drug effects* / Q000473:pathology / Q000503:physiopathology / Q000528:radiation effects*; D012881:Skin Temperature; D013552:Swine; D014018:Tissue Distribution; D014945:Wound Healing
chemical_list: D017319:Photosensitizing Agents; D011524:Protoporphyrins; D000622:Aminolevulinic Acid; C028025:protoporphyrin IX