Effects of β-radiation using a Holmium-166 coated balloon on neointimal hyperplasia in a porcine coronary stent restenosis model

Abstract

Brachytherapy is a promising method of preventing and treating coronary stent restenosis. The present study was designed to observe the therapeutic effects of a radioactive balloon loaded with Holmium-166 (166Ho) in a porcine coronary stent restenosis model. A radioisotope of 166Ho was coated onto the balloon surface using polyurethane (20 Gy at 0.5 mm depth). Stent overdilation injuries were induced in 2 coronary arteries in each pig (n=8). Four weeks after the injury, control balloon dilation was performed in one coronary artery (Group I) and radiation therapy using the 166Ho coated balloon in the other coronary artery (Group II) in each pig. Follow-up coronary angiography and histopathologic assessment were performed at 4 weeks after the radiation therapy or the control balloon dilations. With regard to complete blood cell counts, liver function tests, lipid profiles and coagulation tests, there were no differences between the baseline and after radiation. On quantitative coronary angiographic analysis, reference and target artery diameter showed no differences between the 2 groups before, or 4 and 8 weeks after stenting. On histopathologic analysis of groups I and II, the injury score was 1.34±0.09 and 1.32±0.10, the area of internal elastic lamina was 4.99±0.17 mm2 and 4.82±0.20 mm2, and the luminal area was 3.20±0.10 mm2 and 3.45±0.14 mm2, respectively (p=NS). The neointimal area was 1.78±0.11 mm2 in group I and 1.36±0.12 mm2 in group II (p=0.017), and the histopathologic area of stenosis was 35.1±1.6% in group I and 27.6±1.9% in group II (p=0.005). In conclusion, β-radiation of the stented porcine coronary artery using a radioactive 166Ho coated balloon inhibited stent restenosis without any side effects.