PURE BETA-PARTICLE-EMITTING STENTS INHIBIT NEOINTIMA FORMATION IN RABBITS

Background Considerable experimental evidence exists that neointimal h yperplasia after angioplasty is inhibited by gamma-irradiation of the treated arteries. A beta-particle radiation is absorbed in tissue with in a shorter distance away from the source than gamma-radiation and ma y be more suitable for localized vessel irradiation. This study outlin es a method to implant a beta-particle-emitting radioisotope (P-32; ha lf-life, 14.3 days) into metallic stents. The effects of these stents on the inhibition of neointimal hyperplasia was compared with conventi onal stents in a rabbit model. Methods and Results P-32 was produced b y irradiation of red amorphous phophorus (P-31) with neutrons and was implanted into Palmaz-Schatz stents (7.5 mm in length) after being kep t apart from P-31 in a mass separator. The radioisotope was tightly fi xed to the stents, and the ion implantation process did not alter the surface texture. Stent activity levels of 4 and 13 mu Ci were chosen f or the study. Four and 12 weeks after placement of conventional stents and P-32-implanted stents in rabbit iliac arteries, vascular injury a nd neointima formation were studied by histomorphometry. Immunostainin g for smooth muscle cell (SMC) alpha-actin was performed to determine SMC cellularity in the neointima. SMCs were quantified by computer-ass isted counting of alpha-actin immunoreactive cells. Endothelialization of the stents was evaluated by immunostaining for endothelial cell vo n Willebrand factor. No difference in vessel wall injury was found aft er placement of conventional and P-32-implanted stents. Neointima form ation was potently inhibited by P-32-implanted stents only at an activ ity level of 13 mu Ci after 4 and 12 weeks. Neointimal SMC cellularity was reduced in P-32-implanted stents compared with conventional stent s. Radioactive stents were endothelialized after 4 weeks, but endothel ialization was less dense than in conventional stents. Conclusions Neo intima formation in rabbits is markedly suppressed by a beta-particle- emitting stent incorporating the radioisotope P-32. In this model, a d ose-response relation with this type of radioactive stent was observed , indicating that a threshold radiation dose must be delivered to inhi bit neointima formation after stent placement over the long term.