title: Fractionated illumination after topical application of 5-aminolevulinic acid on normal skin of hairless mice: the influence of the dark interval.
abstract: We have previously shown that light fractionation during topical aminolevulinic acid based photodynamic therapy (ALA-PDT) with a dark interval of 2h leads to a significant increase in efficacy in both pre-clinical and clinical PDT. However this fractionated illumination scheme required an extended overall treatment time. Therefore we investigated the relationship between the dark interval and PDT response with the aim of reducing the overall treatment time without reducing the efficacy. Five groups of mice were treated with ALA-PDT using a single light fraction or the two-fold illumination scheme with a dark interval of 30 min, 1, 1.5 and 2h. Protoporphyrin IX fluorescence kinetics were monitored during illumination. Visual skin response was monitored in the first seven days after PDT and assessed as PDT response. The PDT response decreases with decreasing length of the dark interval. Only the dark interval of 2h showed significantly more damage compared to all the other dark intervals investigated (P<0.05 compared to 1.5h and P<0.01 compared to 1h, 30 min and a single illumination). No relationship could be shown between the utilized PpIX fluorescence during the two-fold illumination and the PDT response. The rate of photobleaching was comparable for the first and the second light fraction and not dependent of the length of dark interval used. We conclude that in the skin of the hairless mouse the dark interval cannot be reduced below 2h without a significant reduction in PDT efficacy.
authors.affiliation: Center for Optical Diagnostics and Therapy, Department of Radiation Oncology, Room Wk-319, Erasmus MC, P.O. Box 2040, 3000 CA Rotterdam, The Netherlands.
authors.forename: H S
authors.initials: HS
authors.lastname: de Bruijn
authors.forename: A
authors.initials: A
authors.lastname: van der Ploeg-van den Heuvel
authors.forename: H J C M
authors.initials: HJ
authors.lastname: Sterenborg
authors.forename: D J
authors.initials: DJ
authors.lastname: Robinson
mesh_terms: D000622:Aminolevulinic Acid / Q000494:pharmacology*; D000818:Animals; D005453:Fluorescence; D007700:Kinetics; D051379:Mice; D008819:Mice, Nude; D038761:Photobleaching / Q000187:drug effects / Q000528:radiation effects*; D010778:Photochemotherapy / Q000379:methods*; D017440:Photoperiod; D017319:Photosensitizing Agents / Q000494:pharmacology*; D011524:Protoporphyrins / Q000032:analysis
chemical_list: D017319:Photosensitizing Agents; D011524:Protoporphyrins; D000622:Aminolevulinic Acid; C028025:protoporphyrin IX