Experimental results with endovascular irradiation via a radioactive stent

Abstract

Purpose : The objective of this article is to describe the methods used to manufacture a radioactive stent and to review the experimental data on this therapy designed to improve arterial patency rates after stent placement. Materials and Methods : Surface activation in a cyclotron and ion implantation techniques are used to render commercially available vascular stents radioactive. β-Particle-emitting stents, most commonly 32P, were employed because of their short half-life (14.3 days) and limited range of tissue penetration (3–4 mm). The function and vascular response to these 32P radioactive stents with varying activities (range 0.14–23 μCi) was evaluated in several animal medels of arterial injury and restenosis. Results : In porcine iliac arteries, β-particle-emitting stents with an initial activity of 0.14 μCi reduced neointimal formation 37% at 28 days after implant. On histology, the neointima consisted of smooth muscle cells and a proteoglycan-rich matrix. Scanning electron microscopy demonstrated complete endothelialization of the stent. β-Particle-emitting stents with an initial activity of 3–23 μCi inhibited neointimal smooth muscle cell proliferation at 28 days in a porcne coronary restenosis model. The neointima within these high-activity stents consisted of fibrin, erythrocytes, and only rare smooth muscle cells. Studies with 1-year follow-up after implantation of a radioactive stent with a composition of γ- and β-particle-emitting radionuclides 55, 56, 57Co, 52Mg, and 55Fe and an initial activity of 17.5 μCi demonstrated almost complete inhibition of neointimal proliferation in a rabbit model. Conclusion : Edovascular irradiation delivered via a radioactive stent reduces neointimal formation and improves luminal patency without increasing the risk for stent thrombosis in experimental models of restenosis. The optimal radiation dose is unknown. At stent activities >3 μCi of 32P, the inhibition of neointimal formation is due to direct radiation affects on proliferating smooth muscle cells. At ultra-low activities (0.14 μCi), β-partcle irradation reduces neointimal formation possibly by impairing cell proliferation or migration. This novel therapy may have a significant impact on preventing stent restenosis, and requires further investigation.