RESUMEN
In the last few years, radioactive stents has been proved to inhibit neointima formation. This paper describes the actual status of producing such radioactive stents. After a short discussion of the different radioisotopes suitable for radioactive stents, potential production methods are discussed. The ion beam implantation of P-32 applied at the Karlsruhe Research Centre shall be described in more detail.
Asunto(s)
Stents , Animales , Enfermedad Coronaria/terapia , Humanos , Ensayo de Materiales , Diseño de Prótesis , Radiactividad , Radioisótopos , Prevención SecundariaRESUMEN
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.
Asunto(s)
Angioplastia de Balón/instrumentación , Partículas beta/uso terapéutico , Braquiterapia/instrumentación , Stents , Animales , Braquiterapia/métodos , Endotelio Vascular/lesiones , Endotelio Vascular/patología , Endotelio Vascular/efectos de la radiación , Estudios de Evaluación como Asunto , Hiperplasia , Arteria Ilíaca/lesiones , Arteria Ilíaca/patología , Arteria Ilíaca/efectos de la radiación , Músculo Liso Vascular/lesiones , Músculo Liso Vascular/patología , Músculo Liso Vascular/efectos de la radiación , Radioisótopos de Fósforo/uso terapéutico , ConejosRESUMEN
BACKGROUND: Restenosis induced by smooth muscle cell (SMC) migration and proliferation and neointimal thickening limits the clinical success of balloon angioplasty and stent implantation. In this study, the long-term effect of endovascular irradiation via low-dose radioactive stents on neointima formation was compared with conventional stent implantation in a rabbit model. METHODS AND RESULTS: Palmaz-Schatz stents were made radioactive in a cyclotron. The stents had a very low activity (maximum, 35 microCi), and thus, manipulation did not require extensive radiation protection. One, 4, 12, and 52 weeks after the implantation of nonradioactive stents and radioactive stents in rabbit iliac arteries, neointimal thickening was analyzed by quantitative histomorphometry. Immunostaining for endothelial cell von Willebrand factor, macrophages, SMC alpha-actin, collagen type I, and proliferating cell nuclear antigen (PCNA) was performed to determine radiation-induced changes in the arterial wall. SMC proliferation was quantified by computer-assisted cell counting of PCNA-immunoreactive cells. Neointima formation was markedly suppressed by the implantation of radioactive stents in a dose-dependent fashion at all observed time points. At peak proliferative activity of SMCs 1 week after nonradioactive stent implantation, 30 +/- 2% of SMCs in the neointima were proliferating, compared with 0.5 +/- 0.1% of SMCs after implantation of stents with an initial activity of 35 microCi (P < .001). The neointima covering radioactive stents was characterized by decreased smooth muscle cellularity and increased extracellular matrix formation. Further, we observed a delayed endothelialization depending on the radiation dose. No difference in vascular thrombosis was found after nonradioactive and radioactive stent implantation. CONCLUSIONS: The results of this study clearly indicate that low-dose radioactive endovascular stents potently inhibit SMC proliferation and neointimal hyperplasia in rabbits.