title: The effect of light fractionation with a 2-h dark interval on the efficacy of topical hexyl-aminolevulinate photodynamic therapy in normal mouse skin.
abstract: BACKGROUND
  Light fractionation with a 2-h dark interval increases the efficacy of topical aminolevulinic acid (ALA) photodynamic therapy (PDT). Hexyl-aminolevulinate (HAL) is the hexyl ester of ALA. Both HAL and ALA lead to protoporphyrin IX (PpIX) accumulation in endothelial cells and to vascular effects, which are important for light fractionation. We investigated light fractionation for HAL-PDT in a mouse skin model and compared this with ALA.
  
  
  METHODS
  Three illumination schemes were studied: (a) 100 J cm(-2) in a single illumination; (b) 50+50 J cm(-2) in a twofold illumination; (c) a small first light fraction until 50% of PpIX was photobleached (ca. 3 J cm(-2)), followed by 97 J cm(-2) 2h later. PpIX fluorescence was measured continuously during illumination. Efficacy was evaluated by daily visual skin damage scoring up to 7 days after PDT.
  
  
  RESULTS
  Light fractionation showed a trend towards increased efficacy for HAL-PDT. Both the initial PpIX synthesis and the PpIX resynthesis during the dark interval were higher for ALA, but these were not correlated with efficacy. Single HAL-PDT was more effective than single ALA-PDT. Photobleaching rates of HAL and ALA were similar indicating similar biodistributions at depth.
  
  
  CONCLUSIONS
  Our results provide evidence to support that light fractionation may be beneficial for HAL-PDT. We are cautious because we found only a non-significant increase in response. However, combining our results with literature data suggest that the illumination scheme may be further optimized for HAL-PDT to potentially enhance the effect of light fractionation.
authors.affiliation: Department of Dermatology, Erasmus MC, Rotterdam, The Netherlands. Electronic address: t.middelburg@erasmusmc.nl.
authors.forename: T A
authors.initials: TA
authors.lastname: Middelburg
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 A M
authors.initials: HA
authors.lastname: Neumann
authors.forename: D J
authors.initials: DJ
authors.lastname: Robinson
mesh_terms: D000287:Administration, Topical; D000622:Aminolevulinic Acid / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000493:pharmacokinetics; D000818:Animals; D019583:Dose Fractionation, Radiation; D008027:Light; D051379:Mice; D008819:Mice, Nude; D010778:Photochemotherapy / Q000379:methods*; D017319:Photosensitizing Agents / Q000008:administration & dosage / Q000493:pharmacokinetics; D012016:Reference Values; D012867:Skin / Q000187:drug effects / Q000378:metabolism* / Q000528:radiation effects*; D016896:Treatment Outcome
chemical_list: D017319:Photosensitizing Agents; D000622:Aminolevulinic Acid; C419924:5-aminolevulinic acid hexyl ester
keywords: ALA; AUC; HAL; Light fractionation; MAL; Mouse skin; PDT; PpIX; SD; aminolevulinic acid; area under the curve; hexyl-aminolevulinate; methyl-aminolevulinate; photodynamic therapy; protoporphyrin IX; standard deviation