title: Molecular imaging of vulnerable plaques in rabbits using contrast-enhanced ultrasound targeting to vascular endothelial growth factor receptor-2.
abstract: OBJECTIVE
  Increased neovascularization has been identified as a feature of atherosclerotic plaque vulnerability and can be traced by microbubble ultrasound contrast agents (UCA). We investigated the relationship between retention of a vascular endothelial growth factor receptor 2 (VEGFR-2) targeted UCA and VEGFR-2 expression in a vulnerable plaque model in rabbits.
  
  
  METHODS
  Microbubbles targeting to VEGFR-2 were prepared by conjugation of biotinylated microbubbles with biotinylated VEGFR-2 antibody via streptavidin. Vulnerability was created by delivering recombinant p53 adenovirus to atherosclerotic plaques obtained in abdominal aorta by a high cholesterol diet and balloon endothelial injury. Twelve week later, the average video intensity of pre- and postcontrast ultrasound images was measured. VEGFR-2 expression and vascular density were quantified by immunohistochemical staining.
  
  
  RESULTS
  Retention of targeted UCA in plaques was higher than that of nontargeted UCA (144 ± 18 dB versus 107 ± 9 dB; Z= -3.984, p = 0.000). VEGFR-2 expression was correlated with video intensity of targeted (r(2) = 0.78, p = 0.001), but not of nontargeted, UCA (r(2) = 0.17, p ≥ 0.05).
  
  
  CONCLUSIONS
  The magnitude of the sonographic signal from retained VEGFR-2 targeted UCA correlates with VEGFR-2 expression. These results validate the use of targeted UCA for sonographic imaging of vulnerable abdominal artery plaques in rabbits.
authors.affiliation: Department of Ultrasound, Second Affiliated Hospital, The Third Military Medical University, Chongqing 400037, PR China.
authors.forename: Hong
authors.initials: H
authors.lastname: Liu
authors.forename: Xiang
authors.initials: X
authors.lastname: Wang
authors.forename: Kai-Bing
authors.initials: KB
authors.lastname: Tan
authors.forename: Ping
authors.initials: P
authors.lastname: Liu
authors.forename: Zhong-Xiong
authors.initials: ZX
authors.lastname: Zhuo
authors.forename: Zheng
authors.initials: Z
authors.lastname: Liu
authors.forename: Xing
authors.initials: X
authors.lastname: Hua
authors.forename: Qin-Qiang
authors.initials: QQ
authors.lastname: Zhuo
authors.forename: Hong-Mei
authors.initials: HM
authors.lastname: Xia
authors.forename: Yun-Hua
authors.initials: YH
authors.lastname: Gao
mesh_terms: D000818:Animals; D003287:Contrast Media; D008297:Male; D045423:Microbubbles; D009389:Neovascularization, Pathologic / Q000000981:diagnostic imaging / Q000378:metabolism; D058226:Plaque, Atherosclerotic / Q000000981:diagnostic imaging* / Q000378:metabolism*; D011817:Rabbits; D014463:Ultrasonography / Q000379:methods; D040301:Vascular Endothelial Growth Factor Receptor-2 / Q000378:metabolism*
chemical_list: D003287:Contrast Media; D040301:Vascular Endothelial Growth Factor Receptor-2