title: Efficacy of contrast-enhanced US and magnetic microbubbles targeted to vascular cell adhesion molecule-1 for molecular imaging of atherosclerosis.
abstract: OBJECTIVE
  To evaluate whether microbubbles targeted to vascular cell adhesion molecule-1 (VCAM-1) (CD106) coupled with a magnetic guidance system could improve the efficacy of contrast-enhanced molecular ultrasonography (US) of atherosclerosis in the aorta.
  
  
  METHODS
  The animal research committee at Southern Medical University approved all experiments. Adherence of magnetic VCAM-1-targeted microbubbles, control inactive magnetic microbubbles, and nonmagnetic VCAM-1-targeted microbubbles to VCAM-1-Fc was determined in vitro by using a flow chamber at variable shear stress (1-24 dyne/cm(2)) under magnetic field guidance. Attachment of microbubbles under magnetic field guidance was determined in vivo with fluorescent microscopy and contrast-enhanced US of the abdominal aorta in wild-type (C57BL/6) or apolipoprotein E (APOE)-deficient mice on a regular or hypercholesterolemic diet. General factorial analysis of variance was used to compare the targeted effect of the microbubbles among different animal groups to identify significant differences.
  
  
  RESULTS
  Attachment was noted for magnetic and nonmagnetic microbubbles but not for inactive magnetic microbubbles; firm attachment at high shear stress (16-20 dyne/cm(2)) was achieved only with magnetic microbubbles. Fluorescence intensity and video intensity were significantly higher in magnetic microbubbles with magnetic field guidance than in inactive magnetic microbubbles and nonmagnetic microbubbles (P < .05). Video intensity from retained magnetic microbubbles in APOE-deficient mice was significantly greater than that in wild-type mice (mean video intensity for APOE-deficient mice: 28.25 [interquartile range, or IQR, 26.55-29.20] with a hypercholesterolemic diet and 16.10 [IQR, 14.15-18.75] with a regular diet; mean video intensity for wild-type mice: 9.55 [IQR, 8.85-10.5] with a hypercholesterolemic diet and 2.90 [IQR, 1.25-3.85] with a regular diet; P < .001).
  
  
  CONCLUSIONS
  Use of a magnetic targeted microbubble system results in greater attachment to endothelial VCAM-1 in atherosclerotic aortas in conditions of high shear stress and improved detection of early inflammatory changes of atherosclerosis.
authors.affiliation: Department of Cardiology, Nanfang Hospital, Southern Medical University, 1838 N Guangzhou Ave, Guangzhou 510515, China.
authors.forename: Juefei
authors.initials: J
authors.lastname: Wu
authors.forename: Howard
authors.initials: H
authors.lastname: Leong-Poi
authors.forename: Jianping
authors.initials: J
authors.lastname: Bin
authors.forename: Li
authors.initials: L
authors.lastname: Yang
authors.forename: Yulin
authors.initials: Y
authors.lastname: Liao
authors.forename: Ying
authors.initials: Y
authors.lastname: Liu
authors.forename: Jingjing
authors.initials: J
authors.lastname: Cai
authors.forename: Jiajia
authors.initials: J
authors.lastname: Xie
authors.forename: Yili
authors.initials: Y
authors.lastname: Liu
mesh_terms: D000704:Analysis of Variance; D000818:Animals; D001018:Aortic Diseases / Q000000981:diagnostic imaging* / Q000378:metabolism*; D050197:Atherosclerosis / Q000000981:diagnostic imaging* / Q000378:metabolism*; D003287:Contrast Media / Q000378:metabolism*; D008280:Magnetics; D051379:Mice; D008817:Mice, Mutant Strains; D045423:Microbubbles; D008856:Microscopy, Fluorescence; D057054:Molecular Imaging / Q000379:methods*; D018709:Statistics, Nonparametric; D014463:Ultrasonography; D019010:Vascular Cell Adhesion Molecule-1 / Q000378:metabolism*
chemical_list: D003287:Contrast Media; D019010:Vascular Cell Adhesion Molecule-1