Cytotoxic effect of photodynamic therapy with photofrin II on intimal hyperplasia

Abstract

This study evaluates the effect of photodynamic therapy using Photofrin II on prevention and treatment of initimal hyperplasia in a rabbit model of common carotid artery balloon injury. An established model was used. One week after injury (inhibition arm) or 6 weeks after injury (treatment arm), each common carotid artery was exposed to continuous external laser irradiation 48 hours after a 5 mg/kg intravenous dose of Photofrin II (fluency=7.6 joules/cm², λ=630 nm). Histologic evaluation was performed 6 weeks following therapy in the inhibition arm and 1 day, 1 week, and 6 weeks following therapy in the treatment arm. Each arm included four subgroups (N=10/subgroup): control, drug only, laser only, and drug plus laser. The first two subgroups underwent sham reoperations without laser exposure. In the inhibition arm no effect was seen on intimal cell density or area stenosis 6 weeks after photodynamic therapy. In the treatment arm intimal cell density was markedly diminished in the drug plus laser subgroup sacrificed 1 day and 1 week (but not 6 weeks) after treatment as compared to the remaining subgroups. There was no significant impact on area of stenosis. A marked acute cytotoxic effect of photodynamic therapy on intimal hyperplasia was verified in vivo in the treatment arm. The extracellular matrix was not affected. Cellular repopulation of the treatment zone was observed. No sustained benefit was seen in either the inhibition or the treatment arm. Refinements in dosimetry will be necessary to achieve long-term benefits.