Experimental results with endovascular irradiation via a radioactive stent

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 models of arterial injury and restenosis. Results: In porcine lilac 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 porcine 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 (55,56,57)Co, ⁵²Mg, and ⁵⁵Fe and an initial activity of 17.5 μCi demonstrated almost complete inhibition of neointimal proliferation in a rabbit model. Conclusion: Endovascular 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-particle irradiation 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.