title: Clearance mechanism of protoporphyrin IX from mouse skin after application of 5-aminolevulinic acid.
abstract: BACKGROUND
  5-Aminolevulinic acid (ALA) or its esters mediated photodynamic therapy (PDT) is the most widely practiced form of PDT in dermatology. One of its advantages is that undesirable photosensitization lasts only for 24-48 h. In order to optimize ALA-PDT it is necessary to understand the mechanisms of intracellular production and clearance of PpIX (efflux from cells into blood stream and/or its conversion into haem). The aim of this study is to investigate the factors controlling the clearance of intracellular PpIX from healthy skin of mice.
  
  
  METHODS
  PpIX was induced in mouse skin by topical or systemic application of ALA or by topical application of the iron chelator ethylenediaminetetraacetic acid (EDTA). Fluorescence spectroscopy was used to study PpIX kinetics in alive and dead skin.
  
  
  RESULTS
  Topical application of ALA or EDTA leads to porphyrin production in living skin, but not in excised skin. The clearance rates of PpIX from alive and dead skin were the same in the absence of an intracellular ALA pool. The clearance half-life of EDTA-induced PpIX was 4-7 times longer than that of PpIX after application of ALA.
  
  
  CONCLUSIONS
  Skin temperature and intracellular iron availability strongly affect PpIX clearance, while ALA application mode (topical versus systemic) and skin viability (dead versus alive) have no influence on PpIX decay. These results demonstrate that the clearance kinetics of PpIX from skin are determined mostly by the conversion of PpIX into haem, while the cellular efflux of PpIX into blood plays a minor role.
authors.affiliation: Department of Radiation Biology, Institute for Cancer Research, Oslo University Hospital, Montebello, 0310 Oslo, Norway. Electronic address: asta.juzeniene@rr-reearch.no.
authors.forename: Asta
authors.initials: A
authors.lastname: Juzeniene
authors.forename: Vladimir
authors.initials: V
authors.lastname: Iani
authors.forename: Johan
authors.initials: J
authors.lastname: Moan
mesh_terms: D000287:Administration, Topical; D000622:Aminolevulinic Acid / Q000008:administration & dosage*; D000818:Animals; D005260:Female; D066298:In Vitro Techniques; D008657:Metabolic Clearance Rate; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D017319:Photosensitizing Agents / Q000008:administration & dosage; D011524:Protoporphyrins / Q000493:pharmacokinetics*; D012867:Skin / Q000187:drug effects* / Q000378:metabolism*; D014018:Tissue Distribution
chemical_list: D017319:Photosensitizing Agents; D011524:Protoporphyrins; D000622:Aminolevulinic Acid; C028025:protoporphyrin IX
keywords: 5-Aminolevulinic acid; 5-aminolevulinic acid; ALA; Ferrochelatase; Fluorescence; PDT; Photodynamic therapy; PpIX; Protoporphyrin IX; photodynamic therapy; protoporphyrin IX; rel. u.; relative units; w/w; weight to weight