Endovascular photodynamic therapy using mono-L-aspartyl-chlorin e6 to inhibit Intimal hyperplasia in balloon-injured rabbit arteries

BACKGROUND AND OBJECTIVE: Intimal hyperplasia (IH) leading to restenosis is a major complication of arterial revascularization. The purpose of this study was to investigate the effect of photodynamic therapy (PDT) using mono-L-aspartyl chlorin e6 (NPe6) as a photosensitizer and intraluminal radial irradiation for inhibition of IH experimentally. STUDY DESIGN/MATERIALS AND METHODS: Study of laser transmission through the blood indicated that exclusion of blood is a prerequisite for intraluminal PDT. For homogeneous radial laser irradiation to the vessel wall, we used a newly developed cylindrical diffusing balloon laser fiber. Injuries were induced by pulling a balloon catheter through the right iliac artery of rabbits. One and 6 hours after the NPe6 injection (5mg/kg i.v.), drug distribution was examined by fluorescence microscopy. Nineteen rabbits received NPe6 at the time of injuries and PDT was performed with 664-nm laser at 30 and 10 J/cm(2) (20, 30, 40 mW/cm(2)) 1 hour after the injuries. The arteries were harvested at 2 days. In a second group of rabbits, PDT was given at 30 mW/cm(2) (30 J/cm(2)). Two weeks after treatment, the arteries were removed and examined histologically. RESULTS: NPe6 was found to be distributed selectively in the injured media. Endovascular NPe6-PDT showed complete depletion of smooth muscle cells even with 10 J/cm(2) at 2 days. IH was significantly inhibited at 14 days after PDT. CONCLUSIONS: Endovascular PDT of injured artery using NPe6 can prevent IH in this model of arterial wall injury and may become clinically useful for the prophylaxis of IH.