Dosage and Timing of Photofrin for Photodynamic Therapy of Intimal Hyperplasia

Photodynamic therapy has been recommended as a method of preventing intimai hyperplasia. The purpose of this study was to determine the dose and timing of Photofrin porfimer sodium needed to achieve a 3:1 or higher ratio between injured and control arteries after balloon endothelial injury. New Zealand White rabbits were anesthetized and their right femoral artery surgically exposed. A 4Fr Fogarty balloon catheter was passed retrograde into the lower abdominal aorta, inflated and pulled distally into the external iliac artery six times. All rabbits received heparin 100 IU/kg. Arteriotomies were closed and the animals recovered. Rabbits (n = 5 per group) were given intravenous Photofrin at a dose and time according to the following scheme: group I, 5.0 mg/kg immediately after balloon injury: group II. 2.5 mg/kg immediately after injury; group III, 5.0 mg/kg after 1 week; group IV, 5.0 mg/kg after 2 weeks; or group V, 2.5 mg/kg after 2 weeks. Animals were killed 24 h after drug administration and the aortoiliac segments removed for spectrophotofluorometric determination of Photofrin levels from injured and control segments. Mean(s.d.) ratios of injured: control arteries for groups I to V were 4.8 (2.6). 2.8 (1.2), 3.0 (1.0), 1.4 (0.3) and 1.0 (0.0) respectively. This ratio was significantly higher for group I rabbits compared with groups IV and V (P<0.01, ANOVA). Fluorescence and light microscopy showed that Photofrin was localized primarily in the tunica media, and that the drug must be administered before significant intimal hyperplasia occurs. This study suggested that the Photofrin dose of 5 mg/kg given immediately or within 7-days of injury achieved at least a 3:1 ratio between injured to control arterial segments. Ratios based on this dose were significantly higher than those from rabbits who received Photofrin 2 weeks after endothelial injury.