title: Topical photodynamic therapy using different porphyrin precursors leads to differences in vascular photosensitization and vascular damage in normal mouse skin.
abstract: Different distributions of hexyl aminolevulinate (HAL), aminolevulinic acid (ALA) and methyl aminolevulinate (MAL) in the superficial vasculature are not well studied but they are hypothesized to play an important role in topical photodynamic therapy (PDT). The colocalization of fluorescent CD31 and protoporphyrin IX (PpIX) was calculated using confocal microscopy of mouse skin sections to investigate the vascular distribution after topical application. Vascular damage leads to disruption of the normal endothelial adherens junction complex, of which CD144 is an integral component. Therefore, normal CD31 combined with loss of normal fluorescent CD144 staining was visually scored to assess vascular damage. Both the vascular PpIX concentration and the vascular damage were highest for HAL, then ALA and then MAL. Vascular damage in MAL was not different from normal contralateral control skin. This pattern is consistent with literature data on vasoconstriction after PDT, and with the hypothesis that the vasculature plays a role in light fractionation that increases efficacy for HAL and ALA-PDT but not for MAL. These findings indicate that endothelial cells of superficial blood vessels synthesize biologically relevant PpIX concentrations, leading to vascular damage. Such vascular effects are expected to influence the oxygenation of tissue after PDT which can be important for treatment efficacy.
authors.affiliation: Department of Dermatology, Erasmus MC, Rotterdam, The Netherlands.
authors.forename: Tom A
authors.initials: TA
authors.lastname: Middelburg
authors.forename: Hannah C
authors.initials: HC
authors.lastname: de Vijlder
authors.forename: Henriette S
authors.initials: HS
authors.lastname: de Bruijn
authors.forename: Angélique
authors.initials: A
authors.lastname: van der Ploeg-van den Heuvel
authors.forename: H A Martino
authors.initials: HA
authors.lastname: Neumann
authors.forename: Ellen R M
authors.initials: ER
authors.lastname: de Haas
authors.forename: Dominic J
authors.initials: DJ
authors.lastname: Robinson
mesh_terms: D000287:Administration, Topical; D000622:Aminolevulinic Acid / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000494:pharmacology*; D000818:Animals; D015703:Antigens, CD; D015820:Cadherins; D042783:Endothelial Cells / Q000187:drug effects / Q000528:radiation effects; D051379:Mice; D010787:Photosensitivity Disorders / Q000139:chemically induced*; D017319:Photosensitizing Agents / Q000008:administration & dosage / Q000494:pharmacology*; D019408:Platelet Endothelial Cell Adhesion Molecule-1 / Q000378:metabolism; D011524:Protoporphyrins / Q000378:metabolism; D012867:Skin / Q000187:drug effects*; D000099152:Cadherin 5
chemical_list: D000622:Aminolevulinic Acid; D015703:Antigens, CD; D015820:Cadherins; D017319:Photosensitizing Agents; D019408:Platelet Endothelial Cell Adhesion Molecule-1; D011524:Protoporphyrins; D000099152:Cadherin 5; C475457:methyl 5-aminolevulinate; C028025:protoporphyrin IX; C419924:5-aminolevulinic acid hexyl ester