THE BETA-PARTICLE-EMITTING RADIOISOTOPE STENT (ISOSTENT) - ANIMAL STUDIES AND PLANNED CLINICAL-TRIALS

Radiation delivered by intravascular stent is an appealing approach to prevent neointimal hyperplasia, since it nonselectively kills dividin g cells. In particular, beta-particle-emitting radioisotope stents may prove to be an ideal means of local irradiation in that 95% of the do se is delivered within 4 mm of the stent edge and the dose drops off r apidly to <1/1,000 of the original dose at 5 months postimplantation. In the in vitro smooth muscle cell model, one can observe a zone of gr owth inhibition around radioactive stent wires that averages about 6 m m at very-low-activity levels (0.006 mu Ci/cm of wire). In vivo studie s in animal models, including porcine iliac and coronary arteries and rabbit iliac arteries, have shown the effectiveness of radioisotope st ents in inhibiting neointimal proliferation. Proliferating endothelial cells appear to be relatively radioresistant. A computer model was em ployed to look at the radiation dose delivered as a function of distan ce from the scent. With very-low-activity stents, presumably, DNA of t he smooth muscle cells is damaged as they migrate through the ''electr on fence'' on the way to the neolumen, diminishing the population of m yofibroblasts and reducing hyperplasia. Catheter-based radiation thera pies may disable these cells before they migrate, although such an app roach may not inhibit early recoil or late contraction. Based on the c haracteristics of beta emissions (i.e., rapid drop-off, minimal leachi ng), radioisotope stents containing phosphorus-32 appear to be safe. A randomized triple-blind clinical trial is planned to assess restenosi s at 6 months in native coronary arteries treated with radioisotope st ents.