Intra-arterial Beta Irradiation Prevents Neointimal Hyperplasia in a Hypercholesterolemic Rabbit Restenosis Model

Abstract

Background Intra-arterial gamma irradiation has been shown to reduce restenosis after balloon angioplasty. The use of beta emitters should allow similar effects while inducing less undue tissue irradiation radioprotection problems. Methods and Results Flexible 90-yttrium ( 90 Y) coils inside a centering balloon were used to allow homogeneous intra-arterial dose delivery. One carotid and one iliac artery of 21 hypercholesterolemic rabbits were deendothelialized and then irradiated. Four dose schedules were studied: (1) control (dilated, nonirradiated); (2) 6 Gy; (3) 12 Gy; and (4) 18 Gy. Arterial specimens were histologically evaluated at 8 days and at 6 weeks. For all radiation doses at 8 days compared with controls, there was a significant decrease in bromodeoxyuridine-labeled cells (245±93 cells/cm in control, 42±27 in 6 Gy, 72±107 in 12 Gy, and 2±2 in 18 Gy groups; P <.001) and in total neointimal cells (891±415 cells/cm in control, 79±43 in 6 Gy, 192±264 in 12 Gy and 22±13 in 18 Gy groups; P <.0002). At 6 weeks, computer-derived histological percent area stenosis was reduced from 26±10% in the control group to 1±1.3% in the 18 Gy group ( P <.0001), but lower doses had no significant effect. Conclusions Administration of intra-arterial beta irradiation with a 90 Y source is technically feasible and compatible with an ordinary catheterization laboratory environment. A dose of 18 Gy effectively induces long-term inhibition of neointimal hyperplasia.