Experimental results with (90)yttrium beta-particle emitting radioactive stents in a porcine model of restenosis

Background: Radioactive stents have been proposed as a means to prevent res tenosis. The ideal radioisotope to deliver endovascular irradiation I ia a radioactive stent is unknown. Objectives: To evaluate the dose response eff ects of "high" dose rate irradiation delivered by a high energy, short half -life, beta-particle emitting (90)ytrrium (Y-90) radioactive stent on neoin timal formation in a porcine coronary model of restenosis. Methods: Fifty-t wo 0-16.0 mu Ci Y-90 radioactive stents were implanted in the coronary arte ries of 19 swine. Stents were oversized 10% to 20% greater than the baselin e angiographic lumen diameter. After 28 days, quantitative histological ana lysis was completed to determine neointimal area and percent in-stent steno sis. Results: The mean vessel injury scores were similar for the control an d each of the Y-90 radioactive stent groups. Neointimal area correlated wit h vessel injury for the control (r = 0.54, P < 0.0001) stents. The percent in-stent stenosis was similar for the nonradioactive control and the 0.25, 0.5, 1.0, 1.25, 2.0, 8.0, and 16.0 mu Ci Y-90 radioactive stents. The neoin timal area was greater for the 4.0 mu Ci (3.95 +/- 1.16 mm(2)) and 8.0 mu C i (3.55 +/- 1.09 mm(2)) Y-90 stents as compared with the nonradioactive con trol stents (2.40 +/- 1.12 mm(2), P less than or equal to 0.03). The increa sed neointimal area for the 4.0 mu Ci Y-90 stents resulted in significantly greater percent in-stent stenosis (55 +/- 12) versus control nonradioactiv e stents (36 +/- 18 P < 0.05). Conclusions: A radioactive stent manufacture d with the short half-life beta-particle emitting radioisotope Y-90, design ed to deliver a higher dose rate at implant than a P-32 radioactive stent, is ineffective in reducing neointimal formation in the porcine coronary mod el of restenosis. Further study is required to define effective cumulative dose and dose rate delivery for radioactive stents.