Gene expression and 18FDG uptake in atherosclerotic carotid plaques.
OBJECTIVE
Metabolic assessment of vascular inflammation by 2-[F]fluoro-2-deoxy-D-glucose positron emission tomography (FDG)-PET is a promising new approach for the evaluation of the vulnerability of atherosclerotic plaques. Quantitative real-time PCR allows measurement of gene expression of markers of atherosclerotic plaque vulnerability. These techniques were applied in advanced atherosclerotic disease to relate metabolism and inflammatory activity to the gene expression profile of the vulnerable atherosclerotic plaque.


METHODS
Seventeen patients with clinical symptoms of cerebral vascular events (<3 months) and an additional ipsilateral internal carotid artery stenosis of greater than 60% were recruited. FDG uptake in the carotids was determined by PET/computed tomography and expressed as mean and maximal standardized uptake values (SUVmean and SUVmax). The atherosclerotic plaques were subsequently recovered by carotid endarterectomy. The gene expression of markers of vulnerability - CD68, IL-18, matrix metalloproteinase 9, cathepsin K, GLUT-1, and hexokinase type II (HK2) - were measured in plaques by quantitative PCR.


RESULTS
In a multivariate linear regression model, GLUT-1, CD68, cathepsin K, and HK2 gene expression remained in the final model as predictive variables of FDG accumulation calculated as SUVmean (R=0.26, P<0.0001). In addition, a multivariate linear regression model found GLUT-1, CD68, cathepsin K, and HK2 gene expression as independent predictive variables of FDG accumulation calculated as SUVmax (R=0.30, P<0.0001).


CONCLUSIONS
GLUT-1, HK2, CD68, and cathepsin K remained in both multivariate models and thus provided independent information regarding FDG uptake. We suggest that FDG uptake is a composite indicator of macrophage load, overall inflammatory activity and collagenolytic plaque destabilization. Accordingly, FDG-PET could prove to be an important predictor of cerebrovascular events in patients with carotid plaques.
Pedersen
Sune Folke
SF
Cluster for Molecular Imaging, Nuclear Medicine and PET, University of Copenhagen, Copenhagen, Denmark. folke@mfi.ku.dk
Graebe
Martin
M
Fisker Hag
Anne Mette
AM
Højgaard
Liselotte
L
Sillesen
Henrik
H
Kjaer
Andreas
A
D000368:Aged; D000369:Aged, 80 and over; D050197:Atherosclerosis / Q000150:complications*; D001692:Biological Transport; D015415:Biomarkers / Q000378:metabolism; D016893:Carotid Stenosis / Q000150:complications / Q000201:enzymology / Q000235:genetics* / Q000378:metabolism*; D005260:Female; D019788:Fluorodeoxyglucose F18 / Q000493:pharmacokinetics*; D020869:Gene Expression Profiling; D006019:Glycolysis; D006801:Humans; D008297:Male; D008875:Middle Aged; D016133:Polymerase Chain Reaction
D015415:Biomarkers; D019788:Fluorodeoxyglucose F18