Dose-response study of intracoronary beta-radiation with ³²P in balloon- and stent-injured coronary arteries in swine

Purpose: A dose-response study was performed in swine to investigate the vascular effects of ³²P over a broad range of doses in order to define the therapeutic window of intracoronary radiotherapy (ICR) with ³²P. Methods and Materials: A total of 131 porcine arteries were subjected to balloon injury or stenting followed by 0-36 Gy of ICR from a centered ³²P source wire to 1 mm beyond lumen surface or a sham ICR procedure. Animals were euthanized at 4 weeks, and vessels were harvested for histomorphometry. Results: In the balloon-injured arteries, doses of 7 and 9 Gy did not impact restenosis. At doses of 14-36 Gy, neointima was markedly reduced, with mild dilatation at the highest dose, 36 Gy. In the stent-injured arteries, the lowest dose of 9 Gy failed to reduce neointimal growth, while 14-26 Gy showed the most favorable response. Conclusions: ICR with ³²P features a broad therapeutic window. Doses of 14-26 Gy to 1 mm beyond lumen surface provided an optimal combination of efficacy and safety. Doses of 7 and 9 Gy were generally ineffective, suggesting a minimum threshold for ICR with ³²P to effectively inhibit restenosis.