18F-FDG PET Imaging of Murine Atherosclerosis: Association with Gene Expression of Key Molecular Markers

Aim: To study whether F-18-FDG can be used for in vivo imaging of atherogenesis by examining the correlation between F-18-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, F-18-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)-1 alpha, HIF-2 alpha, vascular endothelial growth factor A (VEGF), and tissue factor (TF) was measured by means of qPCR. Results: The uptake of F-18-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 F-18-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 F-18-FDG. Together they could explain 60% of the F-18-FDG uptake. Conclusion: We have demonstrated that F-18-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 F-18-FDG. Especially, the gene expressions of CD68, OPN, TF, and VCAM-1 were strong predictors for the uptake.