Prolonged high-fat feeding enhances aortic 18F-FDG and 99mTc-annexin A5 uptake in apolipoprotein E-deficient and wild-type C57BL/6J mice.
(18)F-FDG, a marker of the enhanced metabolism characteristic of activated inflammatory cells, and (99m)Tc-annexin A5, a marker of apoptosis, are both widely believed to be useful for the imaging of unstable atheroma (rupture-prone vulnerable plaques [VP]). Serum cholesterol functions as a proinflammatory factor, driving the formation of VP, and affects the immune responses of aortic tissues systemically. It is therefore reasonable to postulate that prolonged cholesterol loading may alter the aortic uptake of these tracers. Here, we evaluated the aortic uptake of (18)F-FDG and (99m)Tc-annexin A5 in apolipoprotein E-deficient (apoE(-/-)) and wild-type mice placed on high-fat diets.


METHODS
Male apoE(-/-) and wild-type (C57BL/6J) mice were maintained on high-fat diets after the age of 5 wk. Wild-type mice fed regular chow were used as controls. At the ages of 10, 18, and 25 wk (5-15 mice per group at each time point), mice were injected with (18)F-FDG or (99m)Tc-annexin A5 after 12 h of fasting. At 1 h after (18)F-FDG injection (or 2 h after (99m)Tc-annexin A5 injection), mice were sacrificed, and the aortas were removed for well-type scintillation counting of radioactivity. The results were expressed as percentage injected dose per gram of tissue and normalized by animal body weight [(ID%/g) x kg]. En face staining was then performed to assess the location and size (surface area) of the lipid pool within each aortic specimen. Concurrent blood samples were obtained to determine the plasma lipid profile of each group.


RESULTS
No atherosclerotic lesions were found in wild-type mice regardless of the diet, whereas the lesion area progressively increased with age in apoE(-/-) mice. Mean plasma cholesterol levels remained stable with the regular diet in wild-type mice (73-78 mg/dL) but increased with cholesterol feeding in wild-type mice (143-179 mg/dL) and in apoE(-/-) mice (>1,300 mg/dL). Aortic tracer uptake [(ID%/g) x kg] remained stable with the regular diet in wild-type mice (0.054-0.053 and 0.021-0.023 for (99m)Tc-annexin A5) but increased with cholesterol feeding in wild-type mice (0.164 for (18)F-FDG and 0.036 for (99m)Tc-annexin A5 at 25 wk) and in apoE(-/-) mice (0.249 for (18)F-FDG and 0.047 for (99m)Tc-annexin A5 at 25 wk).


CONCLUSIONS
The accumulation of (18)F-FDG and (99m)Tc-annexin A5 in aortic tissues is influenced not only by the progression of atherosclerotic disease but also by cholesterol loading over time.
Zhao
Yan
Y
Department of Nuclear Medicine, Graduate School of Medicine, Hokkaido University, Sapporo, Japan.
Kuge
Yuji
Y
Zhao
Songji
S
Strauss
H William
HW
Blankenberg
Francis G
FG
Tamaki
Nagara
N
D000821:Animal Feed; D000818:Animals; D017304:Annexin A5 / Q000493:pharmacokinetics*; D001011:Aorta / Q000378:metabolism; D001057:Apolipoproteins E / Q000378:metabolism*; D050197:Atherosclerosis / Q000235:genetics / Q000378:metabolism; D001786:Blood Glucose / Q000378:metabolism; D001835:Body Weight; D002784:Cholesterol / Q000097:blood; D004041:Dietary Fats; D019788:Fluorodeoxyglucose F18 / Q000493:pharmacokinetics*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D015609:Organotechnetium Compounds / Q000493:pharmacokinetics*
D017304:Annexin A5; D001057:Apolipoproteins E; D001786:Blood Glucose; D004041:Dietary Fats; D015609:Organotechnetium Compounds; C417036:technetium Tc 99m annexin V; D019788:Fluorodeoxyglucose F18; D002784:Cholesterol