Turku PET Centre, Department of Medicine, Turku University Hospital, and Institute of Forensic Medicine and Turku Center for Disease Modeling, University of Turku, Kiinamyllynkatu 4-8, PO Box 52, FI-20520 Turku, Finland.
Arterioscler Thromb Vasc Biol. 2011 May;31(5):1011-5. doi: 10.1161/ATVBAHA.110.221440. Epub 2011 Mar 3.
Atherosclerotic plaques with large lipid cores and inflammation contain regions of hypoxia. We examined the uptake of 2-(2-nitro-1H-imidazol-1-yl)-N-(2,2,3,3,3-pentafluoropropyl) acetamide ([18F]EF5), a specific marker of hypoxia labeled for positron emission tomography, in mouse atherosclerotic plaques.
Atherosclerotic mice of 2 different genetic backgrounds (low-density lipoprotein receptor-/- apolipoprotein B100/100 and insulin-like growth factor II/low-density lipoprotein receptor-/- apolipoprotein B100/100) were first fed a Western diet to induce development of plaques with variable phenotypes and then injected with [18F]EF5. C57BL/6N mice served as controls. Aortas were dissected for biodistribution studies, autoradiography, histology, and immunohistochemistry. Uptake of [18F]EF5 was significantly higher in the aortas of mice with large atherosclerotic plaques than in the C57BL/6N controls. Furthermore, autoradiography demonstrated, on average, 2.0-fold higher [18F]EF5 uptake in atherosclerotic plaques than in the adjacent normal vessel wall. Hypoxia in plaques was verified by using an EF5 adduct-specific antibody and pimonidazole. The blood clearance of [18F]EF5 was slow, with blood radioactivity remaining relatively high up to 180 minutes after injection.
Large atherosclerotic plaques in mice contained hypoxic areas and showed uptake of [18F]EF5. Despite its slow blood clearance, the high uptake of [18F]EF5 in plaques suggested that plaque hypoxia is a potential target for identifying high-risk plaques noninvasively.
富含大脂质核心和炎症的动脉粥样硬化斑块存在缺氧区域。我们研究了正电子发射断层扫描（PET）用特异性缺氧标志物 2-（2-硝基-1H-咪唑-1-基）-N-（2,2,3,3,3-五氟丙基）乙酰胺（[18F]EF5）在小鼠动脉粥样硬化斑块中的摄取情况。
两种不同遗传背景（载脂蛋白 B100/100 缺失型低密度脂蛋白受体-/-和载脂蛋白 B100/100 缺失型胰岛素样生长因子 II/低密度脂蛋白受体-/-）的动脉粥样硬化小鼠首先给予西方饮食喂养，以诱导具有不同表型的斑块形成，然后注射[18F]EF5。C57BL/6N 小鼠作为对照。对主动脉进行解剖以进行生物分布研究、放射自显影、组织学和免疫组织化学研究。[18F]EF5 的摄取量在载脂蛋白 B100/100 缺失型低密度脂蛋白受体-/-和载脂蛋白 B100/100 缺失型胰岛素样生长因子 II/低密度脂蛋白受体-/-两种动脉粥样硬化小鼠的主动脉中明显高于 C57BL/6N 对照组。此外，放射自显影显示，动脉粥样硬化斑块的[18F]EF5 摄取量平均比相邻正常血管壁高 2 倍。使用 EF5 加合物特异性抗体和 pimonidazole 证实了斑块中的缺氧情况。[18F]EF5 的血液清除缓慢，在注射后 180 分钟内血液放射性仍相对较高。
小鼠的大动脉粥样硬化斑块包含缺氧区域，并显示出[18F]EF5 的摄取。尽管血液清除缓慢，但[18F]EF5 在斑块中的高摄取表明斑块缺氧是一种潜在的靶点，可用于非侵入性地识别高危斑块。
