title: Endovascular irradiation from beta-particle-emitting gold stents results in increased neointima formation in a porcine restenosis model.
abstract: 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 beta-particle-emitting radioactive gold stent and to evaluate the dose-dependent vascular response in the coronary overstretch pig model.
  
  
  RESULTS
  Sixteen Göttinger minipigs underwent placement of 11 nonradioactive and 36 beta-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 microCi of (198)Au. 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 beta-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 beta-particle-emitting stents with (198)Au as the radioisotope. This study provides evidence that dosages of 3 to 18 Gy of low-dose-rate beta-particle irradiation via endovascular stents cause pronounced luminal narrowing in the animal model at 3 months.
authors.affiliation: I. Medizinische Klinik und Poliklinik, Technische Universität München, Germany.
authors.forename: C
authors.initials: C
authors.lastname: Schulz
authors.forename: C
authors.initials: C
authors.lastname: Niederer
authors.forename: C
authors.initials: C
authors.lastname: Andres
authors.forename: R A
authors.initials: RA
authors.lastname: Herrmann
authors.forename: X
authors.initials: X
authors.lastname: Lin
authors.forename: R
authors.initials: R
authors.lastname: Henkelmann
authors.forename: W
authors.initials: W
authors.lastname: Panzer
authors.forename: C
authors.initials: C
authors.lastname: Herrmann
authors.forename: D F
authors.initials: DF
authors.lastname: Regulla
authors.forename: I
authors.initials: I
authors.lastname: Wolf
authors.forename: K
authors.initials: K
authors.lastname: Ulm
authors.forename: E
authors.initials: E
authors.lastname: Alt
mesh_terms: D000818:Animals; D001610:Beta Particles; D003251:Constriction, Pathologic; D017023:Coronary Angiography; D003327:Coronary Disease / Q000473:pathology* / Q000532:radiotherapy*; D004195:Disease Models, Animal; D004307:Dose-Response Relationship, Radiation; D004730:Endothelium, Vascular / Q000473:pathology* / Q000528:radiation effects*; D006050:Gold Radioisotopes / Q000494:pharmacology*; D012008:Recurrence; D015607:Stents; D013552:Swine; D013556:Swine, Miniature; D017539:Tunica Intima / Q000473:pathology / Q000528:radiation effects
chemical_list: D006050:Gold Radioisotopes