In a rabbit model, 32P-implanted stents at an activity level of 13 microCi potently inhibited neointima formation compared with conventional stents at 4 and 12 weeks.
Does a beta-particle-emitting stent (32P) inhibit neointima formation in a rabbit model?
Beta-particle-emitting stents (32P) at a sufficient dose (13 microCi) markedly suppress neointima formation in a rabbit model, suggesting a potential approach to prevent in-stent restenosis.
BACKGROUND: Considerable experimental evidence exists that neointimal hyperplasia after angioplasty is inhibited by gamma-irradiation of the treated arteries. A beta-particle radiation is absorbed in tissue within a shorter distance away from the source than gamma-radiation and may be more suitable for localized vessel irradiation. This study outlines a method to implant a beta-particle-emitting radioisotope (32P; half-life, 14.3 days) into metallic stents. The effects of these stents on the inhibition of neointimal hyperplasia was compared with conventional stents in a rabbit model. METHODS AND RESULTS: 32P was produced by irradiation of red amorphous phophorus (31P) with neutrons and was implanted into Palmaz-Schatz stents (7.5 mm in length) after being kept apart from 31P in a mass separator. The radioisotope was tightly fixed to the stents, and the ion implantation process did not alter the surface texture. Stent activity levels of 4 and 13 microCi were chosen for the study. Four and 12 weeks after placement of conventional stents and 32P-implanted stents in rabbit iliac arteries, vascular injury and neointima formation were studied by histomorphometry. Immunostaining for smooth muscle cell (SMC) alpha-actin was performed to determine SMC cellularity in the neointima. SMCs were quantified by computer-assisted counting of alpha-actin immunoreactive cells. Endothelialization of the stents was evaluated by immunostaining for endothelial cell von Willebrand factor. No difference in vessel wall injury was found after placement of conventional and 32P-implanted stents. Neointima formation was potently inhibited by 32P-implanted stents only at an activity level of 13 microCi after 4 and 12 weeks. Neointimal SMC cellularity was reduced in 32P-implanted stents compared with conventional stents. Radioactive stents were endothelialized after 4 weeks, but endothelialization was less dense than in conventional stents. CONCLUSIONS: Neointima formation in rabbits is markedly suppressed by a beta-particle-emitting stent incorporating the radioisotope 32P. In this model, a dose-response relation with this type of radioactive stent was observed, indicating that a threshold radiation dose must be delivered to inhibit neointima formation after stent placement over the long term.
Hehrlein et al. (Thu,) conducted a other in Neointimal hyperplasia. 32P-implanted stents vs. Conventional stents was evaluated on Neointima formation and smooth muscle cell cellularity. In a rabbit model, 32P-implanted stents at an activity level of 13 microCi potently inhibited neointima formation compared with conventional stents at 4 and 12 weeks.