Feasibility of [18F]-RGD for ex vivo imaging of atherosclerosis in detection of αvβ3 integrin expression
Feasibility of [18F]-RGD for ex vivo imaging of atherosclerosis in detection of αvβ3 integrin expression
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DOI：
10.1007/s12350-014-0061-8
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发表时间：
2015-12-01
影响因子：
2.4
通讯作者：
Slart, Riemer H. J. A.
中科院分区：
文献类型：
--
作者：
Golestani, Reza;Mirfeizi, Leila;Slart, Riemer H. J. A.
背景炎症和血管生成在动脉粥样硬化斑块破裂中起重要作用。因此，这些过程的分子成像可用于确定破裂倾向的动脉粥样硬化斑块。α v β 3整联蛋白参与血管生成过程。在先前的肿瘤模型研究中，使用放射性标记的精氨酸-甘氨酸-天冬氨酸（RGD）对α v β 3整联蛋白进行靶向成像已被证明是可能的。我们的目的是探讨在颈动脉内膜切除术（CEA）标本中体外检测α v β 3整合素的可行性。将19份CEA标本在5 MBq [18 F]-RGD-K5中孵育1小时，然后进行1小时发射microPET扫描。结果以4 mm宽的片段定量为每克孵育剂量百分比（%Inc/g）。计算节段与总比率，并分别通过CD 31和α v β 3整合素的免疫组织化学染色确认每个节段中α v β 3整合素和内皮细胞的存在。[18 F]-RGD-K5摄取在CEA标本中分布不均匀，并定位于血管壁内。片段/总比值与α v β 3整合素染色评分（r = 0.58，P = 0.038）和CD 31染色评分（rho = 0.67，P <0.002）之间存在显著相关性。本研究显示了通过测定人动脉粥样硬化斑块中α v β 3整合素表达进行整合素成像的可行性。
Background. Inflammation and angiogenesis play an important role in atherosclerotic plaque rupture. Therefore, molecular imaging of these processes could be used for determination of rupture-prone atherosclerotic plaques. alpha v beta 3 integrin is involved in the process of angiogenesis. Targeted imaging of alpha v beta 3 integrin has been shown to be possible in previous studies on tumor models, using radiolabeled arginine-glycine-aspartate (RGD). Our aim was to investigate feasibility of ex vivo detection of alpha v beta 3 integrin in carotid endarterectomy (CEA) specimens.Methods and Results. Nineteen CEA specimens were incubated in 5 MBq [18F]-RGD-K5 for 1 hour followed by 1 hour emission microPET scan. The results were quantified in 4 mm wide segments as percent incubation dose per gram (%Inc/g). Segmental-to-total ratio was calculated and presence of alpha v beta 3 integrin and endothelial cells in each segment was confirmed by immunohistochemical staining for CD31 and alpha v beta 3 integrin, respectively. [18F]-RGD-K5 uptake was heterogeneously distributed across CEA specimens and was localized within the vessel wall. Significant correlations were observed between segmental-to-total ratio with alpha v beta 3 integrin staining score (r = 0.58, P = .038) and CD31 staining score (rho = 0.67, P < .002).Conclusion. This study showed the feasibility of integrin imaging by determination of alpha v beta 3 integrin expression in human atherosclerotic plaques.