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首页> 外文期刊>The Journal of Nuclear Medicine >Targeted Folate Receptor β Fluorescence Imaging as a Measure of Inflammation to Estimate Vulnerability Within Human Atherosclerotic Carotid Plaque
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Targeted Folate Receptor β Fluorescence Imaging as a Measure of Inflammation to Estimate Vulnerability Within Human Atherosclerotic Carotid Plaque

机译：有针对性的叶酸受体β荧光成像作为衡量人动脉粥样硬化颈动脉斑块中易损性的一种炎症测量方法

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The probability of atherosclerotic plaque rupture and its thrombotic sequelae are thought to be increased at sites of macrophage accumulation. Folate receptor ?2 (FR-?2) is present on activated macrophages but not on quiescent macrophages or other immune cells. By conjugating the ligand folate with a fluorescent contrast agent, fluorescein isothiocyanate (FITC), we aimed to explore the potential role of FR-?2 fluorescence imaging in the distinction of vulnerable sites from more stable regions. Methods: Carotid specimens were taken from 20 patients and incubated with folatea€“FITC for 30 min. Ex vivo fluorescence imaging was performed to determine the exact location of folatea€“FITC uptake. Sections displaying regions of high uptake (determined as hot spots) were compared with sections showing low uptake (cold spots) through immunohistochemistry and real-time quantitative reverse-transcription polymerase chain reaction for FR-?2. Results: Hot spots showed significantly higher folatea€“FITC uptake than cold spots (P 0.001). Hot spots tended to contain more macrophages and areas of hypoxia than cold spots. A positive correlation between messenger RNA levels of CD68 (marker for macrophages), FR-?2 (r = 0.53, P = 0.045), and hypoxia-inducible factora€“1?± expression (marker for intraplaque hypoxia; r = 0.55, P = 0.034) was found. Conclusion: Compared with areas with low folatea€“FITC uptake, areas of high folatea€“FITC uptake within human atherosclerotic plaques had an increased number of activated macrophages and higher areas of hypoxia. These characteristics of vulnerability imply that molecular imaging of FR-?2 through folate conjugates might be a good indicator for plaque vulnerability in future noninvasive imaging studies.
机译：据认为，在巨噬细胞积累部位，动脉粥样硬化斑块破裂及其血栓后遗症的可能性增加。叶酸受体β2（FR-β2）存在于活化的巨噬细胞上，而不存在于静止的巨噬细胞或其他免疫细胞上。通过将配体叶酸与荧光造影剂异硫氰酸荧光素（FITC）缀合，我们旨在探索FR-β2荧光成像在区分较稳定区域和较脆弱区域中的潜在作用。方法：从20例患者中取出颈动脉标本，并与叶酸FITC孵育30分钟。进行离体荧光成像以确定叶酸-FITC摄取的确切位置。通过免疫组织化学和实时定量逆转录聚合酶链反应对FR-β2，将显示高摄取区域（确定为热点）的区域与显示低摄取区域（冷点）的区域进行比较。结果：热点显示叶酸和FITC的摄入量明显高于冷点（P <0.001）。与冷点相比，热点往往包含更多的巨噬细胞和缺氧区域。 CD68（巨噬细胞标记），FR-α2（r = 0.53，P = 0.045）和缺氧诱导因子α“1α±”表达（斑块内缺氧标记; r = 0.55， P = 0.034）。结论：与低叶酸-FITC摄取区域相比，人动脉粥样斑块中高叶酸-FITC摄取区域具有更多的活化巨噬细胞和较高的缺氧区域。脆弱性的这些特征暗示，通过叶酸结合物对FR-α2进行分子成像可能是未来无创成像研究中斑块脆弱性的良好指标。

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