PHOTODYNAMIC THERAPY - CYTOTOXICITY OF ALUMINUM PHTHALOCYANINE ON INTIMAL HYPERPLASIA

Objective: To study the cytotoxic effect of photodynamic therapy (PDT) on myointimal hyperplasia (MIH) in 120 New Zealand white rabbits usin g the chromophore chloroaluminum phthalocyanine tetrasulfonate (APtS). Design: A common carotid artery (CCA) injury model was used to initia te MIH. Photodynamic therapy was administered 1 week after injury (inh ibition arm) or 6 weeks after injury (treatment arm). The inhibition a rm CCAs were harvested 6 weeks after therapy. The treatment arm CCAs w ere harvested 1 week or 6 weeks after therapy. Each evaluation include d four subgroups (n=10 each): control, drug only, laser only, and drug plus laser. Interventions: An established CCA balloon injury model wa s used. Photodynamic therapy was administered by exposing CCAs to cont inuous external laser irradiation 30 minutes after treatment with a 2. 5-mg/kg intravenous dose of APtS (fluence=25 J/cm(2), lambda=672 nm). The control and drug-only subgroups received sham reoperations without laser exposure. Main Outcome Measures: Following harvest, the CCAs we re evaluated for area of stenosis and cell density. Results: In the in hibition arm, no PDT effect was seen on intimal cell density or area s tenosis. In the treatment arm, intimal cell density was markedly dimin ished (P<.05) in the rabbits in the drug-laser group that were killed 1 week but not 6 weeks after PDT compared with rabbits in the control, drug-only, and laser-only groups. Area stenosis was not significantly affected by PDT. Conclusions: Marked acute cytotoxicity of PDT on MIH was verified in vivo in the treatment arm. No sustained benefit of PD T was seen in the inhibition or the treatment arms. Refinements in dos imetry will be necessary to acheive long-term benefit of PDT for MIH.