Endovascular irradiation from beta-particle-emitting gold stents results in increased neointima formation in a porcine restenosis model

Background-Recent studies have shown that ionizing radiation reduces neoint ima formation after balloon angioplasty and stent implantation in experimen tal models of restenosis and first clinical trials. The objective of this s tudy was to determine the dose distribution of a new beta-particle-emitting radioactive gold stent and to evaluate the dose-dependent vascular respons e in the coronary overstretch pig model. Methods and Results-Sixteen Gottinger minipigs underwent placement of 11 no nradioactive and 36 beta-particle-emitting stents with activity levels of 1 0.4+/-0.6, 14.9+/-2.4, 22.8+/-1.3, 35.8+/-2.8, and 55.4+/-5.3 mu Ci of Au-1 98. Three months after implantation, the percent area stenosis, neointimal thickness, neointimal area, and vessel injury were analyzed by quantitative histomorphometry. The lifetime radiation doses at a depth of 1 mm were 3.3 +/-0.2, 4.7+/-0.5, 7.2+/-0.4, 11.4+/-0.9, and 17.6+/-1.7 Gy for the differe nt activity groups. No dose-response relationship was observed in the radio active stents with respect to percent area stenosis (P=0.297), mean neointi mal thickness (P=0.82), or mean neointimal area (P=0.65). Significantly low er neointima formation and less luminal narrowing was seen in the control g roup than in the beta-particle-emitting stents (P<0.001). Multilinear regre ssion analysis revealed that only radioactivity made a significant independ ent contribution to the degree of percent area stenosis (P<0.001). Conclusions-Neointima formation in pigs is markedly increased by beta-parti cle-emitting stents with Au-198 as the radioisotope. This study provides ev idence that dosages of 3 to 18 Gy of low-dose-rate beta-particle irradiatio n via endovascular stents cause pronounced luminal narrowing in the animal model at 3 months.