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 io implantation techniques are used to render commercially available vascular stents radioactive. beta-Particle-emitting stents, most commonly P-32, 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 P-32 radioactive stents with varying activities (range 0.14-23 mu Ci) was evaluated in several animal models of arterial injury and restenosis. Results: In porcine iliac arteries, beta-particle-emitting stents with an initial activity of 0.14 mu Ci 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, beta-Particle-emitting stents with an initial activity of 3-23 mu Ci 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 gamma- and beta-particle-emitting radionuclides Co-55,Co-56,Co-57, Mg-52, and Fe-55 and an initial activity of 17.5 mu Ci 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 mu Ci of P-32, the inhibition of neointimal formation is due to direct radiation affects on proliferating smooth muscle cells, At ultra-low activities (0.14 mu Ci), beta-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. Published 1996 by Elsevier Science Inc.