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Radiology and Medical Imaging


18F-FDG PET Imaging of Murine Atherosclerosis: Association with Gene Expression of Key Molecular Markers
Published: Friday, November 30, 2012
Author: Anne Mette Fisker Hag et al.

by Anne Mette Fisker Hag, Sune Folke Pedersen, Christina Christoffersen, Tina Binderup, Mette Munk Jensen, Jesper Tranekjær Jørgensen, Dorthe Skovgaard, Rasmus Sejersten Ripa, Andreas Kjaer

Aim

To study whether 18F-FDG can be used for in vivo imaging of atherogenesis by examining the correlation between 18F-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, 18F-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)-1a, HIF-2a, vascular endothelial growth factor A (VEGF), and tissue factor (TF) was measured by means of qPCR.

Results

The uptake of 18F-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 18F-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 18F-FDG. Together they could explain 60% of the 18F-FDG uptake.

Conclusion

We have demonstrated that 18F-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 18F-FDG. Especially, the gene expressions of CD68, OPN, TF, and VCAM-1 were strong predictors for the uptake.

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