title: The phototoxicity of photodynamic therapy may be suppressed or enhanced by modulation of the cutaneous vasculature.
abstract: In photodynamic therapy, the threshold for light induced toxicity depends on the drug concentration and the light dose. This study was aimed to show for vascular photosensitizers that the toxicity threshold on normal tissue may be predictably modified by modulation of the cutaneous vasculature. Albino rabbits were injected with 1.0 mg/kg of a vascular photosensitizer, benzoporphyrin derivative monoacid ring-A. The threshold light dose for toxicity to normal skin was determined at an absorption maximum of the drug (694 nm), 1 h after drug injection. The cutaneous vasculature was dilated by prior skin exposure to ultraviolet radiation or was constricted by iontophoretic application of epinephrine. Threshold toxicity was determined clinically and by assessing the effective concentration of hemoglobin in the skin by diffuse reflectance spectroscopy (DRS). Tissue samples that received threshold doses were investigated with light and electron microscopy. The toxicity threshold increased by 3.2+/-0.9 (mean+/-S.D.) following vasoconstriction and decreased by 3.6+/-0.8 following vasodilation, compared to control sites. Light and electron microscopy showed similar findings at threshold for both vasodilated and vasoconstricted sites. Therefore vascular modulation may be used to predictably enhance or suppress the level of phototoxicity of normal skin.
authors.affiliation: Department of Dermatology, Massachusetts General Hospital, Harvard Medical School, Boston, USA.
authors.forename: S
authors.initials: S
authors.lastname: González
authors.forename: C
authors.initials: C
authors.lastname: Vibhagool
authors.forename: M
authors.initials: M
authors.lastname: Sherwood
authors.forename: T J
authors.initials: TJ
authors.lastname: Flotte
authors.forename: N
authors.initials: N
authors.lastname: Kollias
mesh_terms: D000818:Animals; D017484:Dermatitis, Phototoxic / Q000473:pathology*; D009389:Neovascularization, Pathologic; D010108:Oxyhemoglobins / Q000378:metabolism; D010778:Photochemotherapy; D017319:Photosensitizing Agents / Q000008:administration & dosage / Q000494:pharmacology*; D011166:Porphyrins / Q000008:administration & dosage / Q000494:pharmacology*; D011817:Rabbits; D012867:Skin / Q000098:blood supply* / Q000473:pathology; D000077362:Verteporfin
chemical_list: D010108:Oxyhemoglobins; D017319:Photosensitizing Agents; D011166:Porphyrins; D000077362:Verteporfin