The 90-day coronary vascular response to Y-90-beta particle-emitting stents in the canine model

Purpose: Long-term preclinical studies using continuous, low-dose-rate vasc ular brachytherapy with P-32 beta-emitting stents have yielded largely disa ppointing results. In contrast, a shorter half-life, higher dose-rate Y-90 beta-emitting stent more closely mimics the delivery dose rate characterist ics of clinically effective beta- and gamma-wire and balloon brachytherapy devices. We evaluated the dose response characteristics of a Y-90 beta- emi tting stent in the canine coronary injury model and hypothesized that this device would reduce neointimal formation. Methods: Seventy-seven Y-90 beta-emitting coronary stents (15 mm BXTM, 3.0- and 3.5-mm diameter) were implanted in 26 normal dogs (20-25 kg) using a r andomized, blinded study design. Stent activity included nonradioactive con trols (n = 24), 4.5 mu Ci (n = 15), 8 mu Ci (n = 12), 16 mu Ci (n = 18), an d 32 mu Ci (n = 8). Histologic endpoints were assessed at 3 months. Results: Luminal stenosis and neointimal area were similar in control stent s and low-activity (4.5 and 8 mu Ci) 90Y stents. Higher activity stents (16 and 32 mu Ci) were associated with significant adverse effects. Frequent t otal occlusions (5 of 18 stents, 28%;p = 0.008) and a 40% increase in neoin timal area (p = 0.024 vs. control) occurred in the 16 mu Ci group. Incomple te neointimal healing and a trend for reduced neointimal cell density were evident only in the 16- and 32-mu Ci group. Conclusion: Despite unique characteristics (2.7 day half-life and a higher dose rate) of Y-90 beta-emitting coronary stents, they have an adverse effe ct on neointimal formation, including frequent total occlusions at high act ivity levels. Incomplete healing, present 90 days (33 half-lives) after ste nt placement, indicates prolonged recovery from radiation injury. (C) 2000 Elsevier Science Inc.