ABSTRACT

Despite the benefits of stenting to treat coronary artery disease, in-stent restenosis remains a significant problem, particularly in long lesions and smaller diameter vessels.1 Experimental and clinical data have demonstrated that in-stent restenosis is principally caused by neointimal formation.2 Radiation therapy is known to be effective in reducing benign dermatosis, keloid formation or heterotopic bone formation.3 Studies systematically evaluating the effects of radiation on atherosclerotic arteries began in 1965.4 Later, cell culture studies showed that both migration and proliferation of vascular cells are inhibited by the application of ionizing radiation.5-7 However, depite an obvious therapeutic benefit, many studies showed that ionizing radiation can induce damage to the skin and nearby vascular structures.8 The late effect of, for instance, high volume external beam irradiation is fibrosis, which can cause severe carotid or coronary artery stenosis.9,10 Recently, however, endovascular irradiation has been shown to be a highly effective method of reducing neointimal formation and, thus, preventing restenosis, with excellent midterm results.11,12

Catheter-based irradiation using an 192Ir and a 90Sr/Y source has been effective in reducing neointimal formation after balloon injury, both in a porcine restenosis model and clinically.13,14 An alternative and perhaps simpler approach is the use of a stent as the platform for local radiation delivery as a means to prevent restenosis. Experimental studies have demonstrated that stents ion-implanted with 32P reduce neointimal formation at activities as low as 0.5 µCi.15-17

PROCESSES OF STENT ACTIVATION

There are at least three methods for the fabrication of a radioisotope stent. These include, but are not limited to:

• bombardment of metallic stents with charged particles (i.e. deuterons or protons) • direct ion implantation of stents with radioisotopes • chemical methods for radioisotope incorporation into the metallic stents or stent

coatings.