INHIBITION OF NEOINTIMAL PROLIFERATION WITH LOW-DOSE IRRADIATION FROMA BETA-PARTICLE-EMITTING STENT

Background Restenosis after successful percutaneous trans luminal coro nary angioplasty is the major factor limiting the long-term effectiven ess of this procedure. Neointimal proliferation in response to arteria l injury is an important contributor to restenosis. The use of radiati on for the treatment of malignant and benign proliferative conditions has been well established. External beam irradiation and endovascular irradiation by use of an after-loading technique have been shown to in hibit neointimal proliferation in experimental models of restenosis. T he objective of this study was to investigate whether low-dose irradia tion from a beta-particle-emitting stent would inhibit neointimal prol iferation after placement in porcine iliac arteries. Methods and Resul ts Fourteen titanium-mesh stents were implanted in the iliac arteries of nine NIH miniature swine. There were seven beta-particle-emitting r adioisotope stents (P-32, activity level 0.14 mu Ci) and seven control stents (P-31, nonradioactive). Treatment effect was assessed by angio graphy and histomorphological examination of the stented iliac segment s 28 days after implantation. There was a significant reduction in neo intimal area (1.76+/-0.37 mm(2) versus 2.81+/-1.22 mm(2), P=.05) and p ercent area stenosis (24.6+/-2.9% versus 36.0+/-10.7%, P=.02) within t he beta-particle-emitting stents compared with the control stents. Neo intimal thickness, which was assessed at each wire site, was also sign ificantly less within the treatment stents (0.26+/-0.04 mm versus 0.38 +/-0.10 mm, P=.012). Scanning electron microscopy was performed on sec tions from four stents. This demonstrated endothelialization of both t he treatment and control stents. There was no excess inflammatory reac tion or fibrosis in the media, adventitia, or perivascular space of ve ssels treated with the beta-particle-emitting stent compared with cont rol vessels. At 28 days, there was no difference in smooth muscle cell proliferation as measured by the proliferating cell nuclear antigen i ndex. Conclusions A local, continuous source of low-dose endovascular irradiation via a beta-particle-emitting stent inhibits neointimal for mation in porcine arteries. This low dose of local irradiation did not prevent endothelialization of the stents. This novel technique offers promise for the prevention of restenosis and warrants further investi gation.