The phototoxicity of photodynamic therapy may be suppressed or enhanced bymodulation of the cutaneous vasculature

In photodynamic therapy, the threshold for light induced toxicity depends o n the drug concentration and the light dose. This study was aimed to show f or vascular photosensitizers that the toxicity threshold on normal tissue m ay be predictably modified by modulation of the cutaneous vasculature. Albi no rabbits were injected with 1.0 mg/kg of a vascular photosensitizer, benz oporphyrin derivative monoacid ring-a. The threshold light dose for toxicit y to normal skin was determined at an absorption maximum of the drug (694 n m), 1 h after drug injection. The cutaneous vasculature was dilated by prio r skin exposure to ultraviolet radiation or was constricted by iontophoreti c application of epinephrine. Threshold toxicity was determined clinically and by assessing the effective concentration of hemoglobin in the skin by d iffuse reflectance spectroscopy (DRS). Tissue samples that received thresho ld 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 site s. Light and electron microscopy showed similar findings at threshold for b oth vasodilated and vasoconstricted sites. Therefore vascular modulation ma y be used to predictably enhance or suppress the level of phototoxicity of normal skin. (C) 2000 Elsevier Science S.A. All rights reserved.