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

Background - Recent studies have shown that ionizing radiation reduces neointima formation after balloon angioplasty and stent implantation in experimental models of restenosis and first clinical trials. The objective of this study was to determine the dose distribution of a new β-particle- emitting radioactive gold stent and to evaluate the dose-dependent vascular response in the coronary overstretch pig model. Methods and Results - Sixteen Gottinger minipigs underwent placement of 11 nonradioactive and 36 β- particle-emitting stents with activity levels of 10.4±0.6, 14.9±2.4, 22.8± 1.3, 35.8±2.8, and 55.4±5.3 μCi of ¹⁹⁸Au. 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 different activity groups. No dose-response relationship was observed in the radioactive stents with respect to percent area stenosis (P=0.297), mean neointimal thickness (P=0.82), or mean neointimal area (P=0.65). Significantly lower neointima formation and less luminal narrowing was seen in the control group than in the β-particle-emitting stents (P<0.001). Multilinear regression analysis revealed that only radioactivity made a significant independent contribution to the degree of percent area stenosis (P<0.001). Conclusions - Neointima formation in pigs is markedly increased by β-particle-emitting stents with ¹⁹⁸Au as the radioisotope. This study provides evidence that dosages of 3 to 18 Gy of low-dose-rate β-particle irradiation via endovascular stents cause pronounced luminal narrowing in the animal model at 3 months.