Abstract
Objectives: Vulnerability of atheroma is associated with activated macrophage infiltration and apoptosis of foam cells. Activated macrophages have a high metabolic rate, and utilize exogenous glucose as their energy source. The oxidized lipid content of foam cells, is toxic and often results in apoptosis of these cells. Nuclear imaging provides at least two potential indicators to identify vulnerable plaques: 18 F-FDG as a marker of macrophage metabolism and 99m Tc-annexin A5 ( 99m Tc-AN5) as a marker of apoptosis. This study compared the macrophage infiltration and lesion histology to the uptake of each tracer in apolipoprotein E knockout (ApoE−/−) mice. Methods: Male apoE−/− mice (n=4 –5/group) were maintained on a high-fat diet after the age of 5 wks. At the age of 25 and 35 wks, 14 C-FDG and 99m Tc-AN5 were administered and aortas were harvested. Dual-tracer autoradiography, Movat pentachrome staining and Mac-2 staining were performed on serial cryostat sections (n=5– 6/mouse). Regional tracer uptake levels (ID%×kg/mm 2 ) were evaluated in relation to the morphological lesion characteristics (AHA lesion phenotypes) and degree of macrophage infiltration (Mac-2 positive areas). Results: Plaque size and intimal thickness were increased with lesion progression. Macrophage infiltration was increased from early (type I-II) to atheromatous lesions (type III-IV) but decreased in fibroatheromatous lesions (type V). 99m Tc-AN5 showed higher uptake levels in atheromatous lesions (0.49±0.20 %IDxkg/mm 2 ) than early (0.40±0.17) or fibroatheromatous (0.30±0.13) lesions, being concordant with macrophage infiltration. 14 C-FDG uptake was also the highest in atheromatous lesions (3.1±1.5 in atheromatous, 2.8±1.5 in early, and 2.3±1.4 in fibroatheromatous lesions). The uptakes of both 99m Tc-AN5 (r=0.65, p<0.01) and 14 C-FDG (r=0.44, p<0.001) were positively correlated with the degrees of macrophage infiltration. Conclusion: Each tracer showed a higher uptake in atheromatous lesions (AHA type III-IV) than other more stable lesions, directly corresponding to the degree of macrophage infiltration. Unstable plaques can be imaged utilizing 18 F-FDG and 99m Tc-annexin A5, due to the presence of metabolically active and apoptotic macrophages.
Published Version
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