Experimental results with endovascular irradiation via a radioactive stent.
OBJECTIVE
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.


METHODS
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.


RESULTS
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.


CONCLUSIONS
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.
Carter
A J
AJ
Cardiology Service, Walter Reed Army Medical Center, Washington, DC 20307-5001, USA.
Laird
J R
JR
D000818:Animals; D001918:Brachytherapy / Q000295:instrumentation*; D003331:Coronary Vessels / Q000473:pathology / Q000528:radiation effects*; D004730:Endothelium, Vascular / Q000473:pathology / Q000528:radiation effects*; D004867:Equipment Design; D007083:Iliac Artery / Q000473:pathology / Q000528:radiation effects*; D009131:Muscle, Smooth, Vascular / Q000473:pathology / Q000528:radiation effects*; D010761:Phosphorus Radioisotopes; D015607:Stents; D013552:Swine; D014654:Vascular Patency
D010761:Phosphorus Radioisotopes