Prolonged High-Fat Feeding Enhances Aortic 18F-FDG and 99mTc-Annexin A5 Uptake in Apolipoprotein E-Deficient and Wild-Type C57BL/6J Mice
Prolonged High-Fat Feeding Enhances Aortic 18F-FDG and 99mTc-Annexin A5 Uptake in Apolipoprotein E-Deficient and Wild-Type C57BL/6J Mice
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DOI：
10.2967/jnumed.108.051847
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发表时间：
2008-10-01
影响因子：
9.3
通讯作者：
Tamaki, Nagara
中科院分区：
文献类型：
--
作者：
Zhao, Yan;Kuge, Yuji;Tamaki, Nagara
F-18-FDG 是活化炎症细胞代谢增强特征的标志物，而 Tc-99m-annexin A5 是细胞凋亡标志物，两者都被广泛认为可用于不稳定动脉粥样硬化斑块（易破裂的易损斑块 [VP]）的成像。血清胆固醇作为促炎因子发挥作用，驱动VP的形成，并影响主动脉组织的全身免疫反应。因此，可以合理地假设，长期胆固醇负荷可能会改变这些示踪剂的主动脉摄取。在这里，我们评估了载脂蛋白 E 缺陷 (apoE(-/-)) 和高脂肪饮食的野生型小鼠的主动脉对 F-18-FDG 和 99mTc-annexin A5 的摄取。方法：雄性 apoE(-/-) 和野生型 (C57BU6J) 小鼠在 5 周龄后维持高脂肪饮食。使用常规饲料喂养的野生型小鼠作为对照。在10周、18周和25周龄（每个时间点每组5-15只小鼠），小鼠禁食12小时后注射18F-FDG或99mTc-annexin A5。注射 F-18-FDG 1 小时后（或注射 99"Tc-annexin A5 后 2 小时），处死小鼠，取出主动脉进行放射性孔型闪烁计数。结果表示为每克组织注射剂量的百分比，并通过动物体重标准化 [(ID%/g) x kg]。然后进行 En 面染色以评估每个主动脉内脂质池的位置和大小（表面积）结果：无论饮食如何，野生型小鼠均未发现动脉粥样硬化病变，而 apoE(-/-) 小鼠的病变面积随着年龄的增长而逐渐增加，野生型小鼠的平均血浆胆固醇水平在常规饮食下保持稳定 (73-78 mg/dL)，但在野生型小鼠 (143-179 mg/dL) 和小鼠中，随着胆固醇喂养而增加。 apoE(-/-) 小鼠 (>1,300 mg/dL)。野生型小鼠的主动脉示踪剂摄取量 [(ID%/g) x kg] 与常规饮食保持稳定（Tc-99m-annexin A5 为 0.054-0.053 和 0.021-0.023），但在野生型小鼠中随着胆固醇喂养而增加（F-18-FDG 为 0.164，F-18-FDG 为 0.164）。 25 周时 Tc-99m-annexin A5 为 0.036) 和 apoE(-/-) 小鼠（25 周时 F-18-FDG 为 0.249，Tc-99m-annexin A5 为 0.047） 结论：主动脉组织中 18F-FDG 和 99mTc-annexin A5 的积累不仅受到疾病进展的影响。动脉粥样硬化疾病还与胆固醇负荷超时有关。
F-18-FDG, a marker of the enhanced metabolism characteristic of activated inflammatory cells, and Tc-99m-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 F-18-FDG and 99mTc-annexin A5 in apolipoprotein E-deficient (apoE(-/-)) and wild-type mice placed on high-fat diets. Methods: Male apoE(-/-) and wild-type (C57BU6J) 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 18F-FDG or 99mTc-annexin A5 after 12 h of fasting. At 1 h after F-18-FDG injection (or 2 h after 99"'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 Tc-99m-annexin A5) but increased with cholesterol feeding in wild-type mice (0.164 for F-18-FDG and 0.036 for Tc-99m-annexin A5 at 25 wk) and in apoE(-/-) mice (0.249 for F-18-FDG and 0.047 for Tc-99m-annexin A5 at 25 wk). Conclusion: The accumulation of 18F-FDG and 99mTc-annexin A5 in aortic tissues is influenced not only by the progression of atherosclerotic disease but also by cholesterol loading overtime. Key Words: atherosclerosis; apoptosis; inflammation; serum cholesterol levels