Localization of deoxyglucose and annexin a5 in experimental atheroma correlates with macrophage infiltration but not lipid deposition in the lesion

Purpose: The aim of this study was to understand the relationship of lipid deposition to the macrophage content, macrophage metabolism, and apoptosis in plaque. We compared the uptake of 2-deoxy-2-fluoro-D-[¹⁴C]glucose ([¹⁴C]FDG) and [99m^Tc]HYNIC-annexin V ([99m^Tc] annexin A5) with the lesion histology in apolipoprotein E knockout (apoE ^-/-) mice. Procedures: Male apoE^-/- mice (n=9) were injected with [¹⁴C]FDG and [99m^Tc]annexin A5. Cryostat sections of aorta samples (n=49) were used for dual-tracer autoradiography, and regional tracer uptake levels were evaluated. Lesions were identified histologically with Movat's pentachrome (AHA lesion phenotypes), Mac-2 staining (macrophage infiltration) and Oil Red O staining (lipid deposition). Results: The highest uptakes of [¹⁴C]FDG (3.10±1.50 %ID×kilogram per square millimeter) and [99m^Tc]annexin A5 (0.49±0.20 %ID×kilogram per square millimeter) were shown in atheromatous lesions (types III and IV). Each tracer uptake showed better correlation with macrophage infiltration than lipid deposition ([¹⁴C]FDG, r=0.44 vs. r=0.14; [99m^Tc]annexin A5, r=0.65 vs. r=0.48). Conclusions: Both tracers were concentrated in type III and IV atheromatous lesions which corresponded to macrophage infiltration rather than lipid deposition.