Hehrlein C, Stintz M, Kinscherf R, Schlösser K, Huttel E, Friedrich L, Fehsenfeld P, Kübler W
Department of Cardiology, University of Heidelberg, Germany.
Circulation. 1996 Feb 15;93(4):641-5. doi: 10.1161/01.cir.93.4.641.
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.
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.
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.
有大量实验证据表明，血管成形术后的新生内膜增生可通过对治疗动脉进行γ射线照射来抑制。β粒子辐射在组织中的吸收距离比γ射线离源更近，可能更适合局部血管照射。本研究概述了一种将发射β粒子的放射性同位素（32P；半衰期为14.3天）植入金属支架的方法。在兔模型中，将这些支架对新生内膜增生的抑制作用与传统支架进行了比较。
通过用中子照射红色无定形磷（31P）产生32P，并在质量分离器中与31P分离后将其植入Palmaz-Schatz支架（长度为7.5 mm）。放射性同位素紧密固定在支架上，离子注入过程未改变表面纹理。选择4和13微居里的支架活性水平进行研究。在兔髂动脉中植入传统支架和32P植入支架4周和12周后，通过组织形态计量学研究血管损伤和新生内膜形成。进行平滑肌细胞（SMC）α-肌动蛋白免疫染色以确定新生内膜中的SMC细胞数量。通过计算机辅助计数α-肌动蛋白免疫反应细胞对SMC进行定量。通过对内皮细胞血管性血友病因子进行免疫染色来评估支架的内皮化。植入传统支架和32P植入支架后，未发现血管壁损伤有差异。仅在4周和12周后，活性水平为13微居里的32P植入支架才有效抑制新生内膜形成。与传统支架相比，32P植入支架中的新生内膜SMC细胞数量减少。放射性支架在4周后内皮化，但内皮化程度不如传统支架密集。
含有放射性同位素32P的发射β粒子的支架可显著抑制兔新生内膜形成。在该模型中，观察到了这种类型的放射性支架的剂量反应关系，表明必须给予阈值辐射剂量才能长期抑制支架植入后的新生内膜形成。
