title: (18)F-FDG PET imaging of murine atherosclerosis: association with gene expression of key molecular markers.
abstract: OBJECTIVE
  To study whether (18)F-FDG can be used for in vivo imaging of atherogenesis by examining the correlation between (18)F-FDG uptake and gene expression of key molecular markers of atherosclerosis in apoE(-/-) mice.
  
  
  METHODS
  Nine groups of apoE(-/-) mice were given normal chow or high-fat diet. At different time-points, (18)F-FDG PET/contrast-enhanced CT scans were performed on dedicated animal scanners. After scans, animals were euthanized, aortas removed, gamma counted, RNA extracted from the tissue, and gene expression of chemo (C-X-C motif) ligand 1 (CXCL-1), monocyte chemoattractant protein (MCP)-1, vascular cell adhesion molecule (VCAM)-1, cluster of differentiation molecule (CD)-68, osteopontin (OPN), lectin-like oxidized LDL-receptor (LOX)-1, hypoxia-inducible factor (HIF)-1α, HIF-2α, vascular endothelial growth factor A (VEGF), and tissue factor (TF) was measured by means of qPCR.
  
  
  RESULTS
  The uptake of (18)F-FDG increased over time in the groups of mice receiving high-fat diet measured by PET and ex vivo gamma counting. The gene expression of all examined markers of atherosclerosis correlated significantly with (18)F-FDG uptake. The strongest correlation was seen with TF and CD68 (p<0.001). A multivariate analysis showed CD68, OPN, TF, and VCAM-1 to be the most important contributors to the uptake of (18)F-FDG. Together they could explain 60% of the (18)F-FDG uptake.
  
  
  CONCLUSIONS
  We have demonstrated that (18)F-FDG can be used to follow the progression of atherosclerosis in apoE(-/-) mice. The gene expression of ten molecular markers representing different molecular processes important for atherosclerosis was shown to correlate with the uptake of (18)F-FDG. Especially, the gene expressions of CD68, OPN, TF, and VCAM-1 were strong predictors for the uptake.
authors.affiliation: Cluster for Molecular Imaging, Faculty of Health and Medical Sciences and Department of Clinical Physiology, Nuclear Medicine & PET, Rigshospitalet, University of Copenhagen, Copenhagen, Denmark. annemf@sund.ku.dk
authors.forename: Anne Mette Fisker
authors.initials: AM
authors.lastname: Hag
authors.forename: Sune Folke
authors.initials: SF
authors.lastname: Pedersen
authors.forename: Christina
authors.initials: C
authors.lastname: Christoffersen
authors.forename: Tina
authors.initials: T
authors.lastname: Binderup
authors.forename: Mette Munk
authors.initials: MM
authors.lastname: Jensen
authors.forename: Jesper Tranekjær
authors.initials: JT
authors.lastname: Jørgensen
authors.forename: Dorthe
authors.initials: D
authors.lastname: Skovgaard
authors.forename: Rasmus Sejersten
authors.initials: RS
authors.lastname: Ripa
authors.forename: Andreas
authors.initials: A
authors.lastname: Kjaer
mesh_terms: D000818:Animals; D050197:Atherosclerosis / Q000000981:diagnostic imaging* / Q000235:genetics*; D015415:Biomarkers / Q000378:metabolism*; D019788:Fluorodeoxyglucose F18 / Q000493:pharmacokinetics; D005786:Gene Expression Regulation; D016014:Linear Models; D051379:Mice; D015999:Multivariate Analysis; D049268:Positron-Emission Tomography; D014057:Tomography, X-Ray Computed
chemical_list: D015415:Biomarkers; D019788:Fluorodeoxyglucose F18