Effectiveness of radioactive tungsten source in the prevention of restenosis in stented porcine coronary arteries

Abstract

Purpose : Intracoronary radiation has shown the potential to inhibit neointimal proliferation in porcine models of restenosis. The objective of this study was to determine whether intracoronary radiation using a new coiled wire of tungsten-188 ( 188W), a pure β emitter (half-life 69.4 days) is safe. In addition, a dose of 0 Gy, 18 Gy, or 25 Gy prescribed to 2 mm from the center of the source and delivered intraluminally is sufficient to prevent restenosis and free from adverse effects. Methods and Materials : Ten domestic swine underwent 13-mm stent implantation (SI) into two arteries, left anterior descending plus either the left circumflex or right coronary artery. After SI, a closed-end lumen radiation catheter was inserted to the treated artery and a 40-mm coiled 188W source was manually delivered to cover the stented segment and its margins. A total of 20 arteries were randomized to treatment with a radiation dose of 0, 18 Gy, or 25 Gy delivered to 2 mm depth from the center of the source. Four weeks after the procedure, the swine underwent angiography and intravascular ultrasound using automated pullback at 0.5 mm/s. before being killed and the arteries perfusion fixed. Histopathologic and histomorphometric analyses were performed at 28 days after injury and radiation. Results : Irradiation with 188W at a dose of 25 Gy after SI significantly inhibited neointima formation (intimal area: 1.05 ± 0.64 vs. 2.75 ± 0.99 mm 2, p < 0.01) and at an 18 Gy dose of radiation (intimal area: 1.73 ± 0.49 vs. 2.75 ± 0.99 mm 2), as compared to controls. One artery receiving 18 Gy and two arteries receiving 25 Gy were totally occluded at follow-up due to thrombus formation but no edge stenosis was observed in any of the irradiated arteries. Conclusions : Intracoronary radiation therapy using a new coiled wire of 188W source delivered after SI appeared to be safe and well tolerated. The radiation doses demonstrated efficacy in reducing neointima formation in the porcine coronary stent injury model.