Carter A J, Laird J R
Cardiology Service, Walter Reed Army Medical Center, Washington, DC 20307-5001, USA.
Int J Radiat Oncol Biol Phys. 1996 Nov 1;36(4):797-803. doi: 10.1016/s0360-3016(96)00410-5.
The objective of this article is to describe the methods used to manufacture a radioactive stent and to review the experimental data on this therapy designed to improve arterial patency rates after stent placement.
Surface activation in a cyclotron and ion implantation techniques are used to render commercially available vascular stents radioactive. beta-Particle-emitting stents, most commonly 32P, were employed because of their short half-life (14.3 days) and limited range of tissue penetration (3-4 mm). The function and vascular response to these 32P radioactive stents with varying activities (range 0.14-23 microCi) was evaluated in several animal models of arterial injury and restenosis.
In porcine iliac arteries, beta-particle-emitting stents with an initial activity of 0.14 microCi reduced neointimal formation 37% at 28 days after implant. On histology, the neointima consisted of smooth muscle cells and a proteoglycan-rich matrix. Scanning electron microscopy demonstrated complete endothelialization of the stent. beta-Particle-emitting stents with an initial activity of 3-23 microCi inhibited neointimal smooth muscle cell proliferation at 28 days in a porcine coronary restenosis model. The neointima within these high-activity stents consisted of fibrin, erythrocytes, and only rare smooth muscle cells. Studies with 1-year follow-up after implantation of a radioactive stent with a composition of gamma- and beta-particle-emitting radionuclides 55,56,57Co, 52Mg, and 55Fe and an initial activity of 17.5 microCi demonstrated almost complete inhibition of neointimal proliferation in a rabbit model.
Endovascular irradiation delivered via a radioactive stent reduces neointimal formation and improves luminal patency without increasing the risk for stent thrombosis in experimental models of restenosis. The optimal radiation dose is unknown. At stent activities >3 microCi of 32P, the inhibition of neointimal formation is due to direct radiation affects on proliferating smooth muscle cells. At ultra-low activities (0.14 microCi), beta-particle irradiation reduces neointimal formation possibly by impairing cell proliferation or migration. This novel therapy may have a significant impact on preventing stent restenosis, and requires further investigation.
本文的目的是描述制造放射性支架所使用的方法，并回顾关于这种旨在提高支架置入后动脉通畅率的治疗方法的实验数据。
利用回旋加速器中的表面活化和离子注入技术使市售血管支架具有放射性。使用发射β粒子的支架，最常见的是32P，因为其半衰期短（14.3天）且组织穿透范围有限（3 - 4毫米）。在几种动脉损伤和再狭窄的动物模型中评估了这些具有不同活度（范围为0.14 - 23微居里）的32P放射性支架的功能和血管反应。
在猪髂动脉中，初始活度为0.14微居里的发射β粒子的支架在植入后28天时使新生内膜形成减少37%。组织学检查显示，新生内膜由平滑肌细胞和富含蛋白聚糖的基质组成。扫描电子显微镜显示支架完全内皮化。在猪冠状动脉再狭窄模型中，初始活度为3 - 23微居里的发射β粒子的支架在28天时抑制了新生内膜平滑肌细胞增殖。这些高活度支架内的新生内膜由纤维蛋白、红细胞和极少的平滑肌细胞组成。对一种由发射γ和β粒子的放射性核素55、56、57Co、52Mg和55Fe组成且初始活度为17.5微居里的放射性支架植入后进行的1年随访研究表明，在兔模型中新生内膜增殖几乎完全受到抑制。
在再狭窄的实验模型中，通过放射性支架进行血管内照射可减少新生内膜形成并改善管腔通畅性，而不会增加支架血栓形成的风险。最佳辐射剂量尚不清楚。当支架活度>3微居里的32P时，对新生内膜形成的抑制是由于对增殖平滑肌细胞的直接辐射作用。在超低活度（0.14微居里）时，β粒子照射可能通过损害细胞增殖或迁移来减少新生内膜形成。这种新疗法可能对预防支架再狭窄有重大影响，需要进一步研究。
