title: Dose and timing of the first light fraction in two-fold illumination schemes for topical ALA-mediated photodynamic therapy of hairless mouse skin.
abstract: A fractionated illumination scheme in which a cumulative fluence of 100 J cm(-2) is delivered in two equal light fractions separated by a dark interval of 2 h has been shown to considerably increase the efficacy of 5-aminolevulinic acid (ALA)-photodynamic therapy (PDT). The efficacy of such a scheme is further increased if the fluence of the first light fraction is reduced to 5 J cm(-2). We have investigated the relationship between the PDT response and the kinetics of protoporphyrin IX (PpIX) fluorescence in the SKH1 HR hairless mouse for first fraction fluences below 5 J cm(-2) delivered 4 h after the application of ALA and 10 J cm(-2) delivered 2 h after the application of ALA. Illumination is performed using 514 nm at a fluence rate of 50 mW cm(-2). Reducing the fluence of the first fraction to 2.5 J cm(-2) does not result in significantly different visual skin damage. The PDT response, however, is significantly reduced if the fluence is lowered to 1 J cm(-2), but this illumination scheme (1 + 99 J cm(-2)) remains significantly more effective than a single illumination of 100 J cm(-2). A first light fraction of 10 J cm(-2) can be delivered 2 h earlier, 2 h after the application of ALA, without significant reduction in the PDT response compared with 5 + 95 J cm(-2) delivered 4 and 6 h after the application of ALA. The kinetics of PpIX fluorescence are consistent with those reported previously by us and do not explain the significant increase in PDT response with a two-fold illumination scheme. Histological sections of the illuminated volume showed a trend toward increasing extent and depth of necrosis for the two-fold illumination scheme in which the first light fraction is 5 J cm(-2), compared with a single illumination scheme.
authors.affiliation: Photodynamic Therapy and Optical Spectroscopy Research Program, Department of Radiation Oncology, Erasmus MC: Daniel den Hoed Cancer Center, Rotterdam, The Netherlands. robinson@kfih.azr.nl
authors.forename: Dominic J
authors.initials: DJ
authors.lastname: Robinson
authors.forename: Henriëtte S
authors.initials: HS
authors.lastname: de Bruijn
authors.forename: Willem M
authors.initials: WM
authors.lastname: Star
authors.forename: Henricus J C M
authors.initials: HJ
authors.lastname: Sterenborg
mesh_terms: D000622:Aminolevulinic Acid / Q000008:administration & dosage; D000818:Animals; D005260:Female; D007700:Kinetics; D051379:Mice; D008812:Mice, Hairless; D009336:Necrosis; D010778:Photochemotherapy / Q000009:adverse effects / Q000379:methods*; D017319:Photosensitizing Agents / Q000008:administration & dosage; D011524:Protoporphyrins / Q000378:metabolism; D012867:Skin / Q000187:drug effects / Q000378:metabolism / Q000473:pathology / Q000528:radiation effects
chemical_list: D017319:Photosensitizing Agents; D011524:Protoporphyrins; D000622:Aminolevulinic Acid; C028025:protoporphyrin IX