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18F-PBR06正电子发射断层显像/X线计算机体层成像(PET/CT)用于评估与巨噬细胞浸润相关的动脉粥样硬化斑块。

18F-PBR06 PET/CT imaging for evaluating atherosclerotic plaques linked to macrophage infiltration.

作者信息

Zhang He, Xiao Jie, Zhou Jun, Tan Hui, Hu Yan, Mao Wujian, Fu Zhequan, Lin Qingyu, Shi Hongcheng, Cheng Dengfeng

机构信息

Department of Nuclear Medicine, Zhongshan Hospital.

Shanghai Institute of Medical Imaging.

出版信息

Nucl Med Commun. 2019 Apr;40(4):370-376. doi: 10.1097/MNM.0000000000000978.

Abstract

BACKGROUND

The present study explored the 18 kDa translocator protein radioligand [F]N-fluoroacetyl-N-(2,5-dimethoxybenzyl)-2-phenoxyaniline (F-PBR06) targeting macrophages for PET imaging of atherosclerotic plaques and evaluating the vulnerability of atherosclerotic plaques toward rupture.

MATERIALS AND METHODS

F-PBR06 was synthesized using a Synthra RNplus module automatically. RAW264.7 cells were used for cell binding study with F-PBR06. In-vivo micro-PET/CT imaging for ApoE mice and C57 mice was performed 1 h after injection of F-PBR06. CD68 and F480 immunofluorescence stainings were performed in the aorta tissues.

RESULTS

In-vitro cell studies showed uptake of F-PBR06 to RAW264.7 cells. Micro-PET/CT imaging identified the atherosclerotic lesions in the aortic arch of ApoE mice successfully, whereas no signal was observed in C57 mice. The ratio of plaque-to-muscle in ApoE mice of 32 weeks was significantly higher than that in ApoE mice of 22 weeks, which was confirmed by CD68 immunofluorescence staining and F480 immunofluorescence staining.

CONCLUSION

TSPO radioligand F-PBR06 allows noninvasive PET/CT imaging of macrophage-abundant atherosclerotic plaques as well as positive correlation between PET imagings and ex-vivo immunofluorescence staining of plaques in mice with different ages, thereby representing a potential attractive tool for evaluating the vulnerability of atherosclerotic plaques towards rupture.

摘要

背景

本研究探索了靶向巨噬细胞的18 kDa转位蛋白放射性配体[F]N-氟乙酰基-N-(2,5-二甲氧基苄基)-2-苯氧基苯胺(F-PBR06),用于动脉粥样硬化斑块的PET成像以及评估动脉粥样硬化斑块破裂的易损性。

材料与方法

使用Synthra RNplus模块自动合成F-PBR06。采用RAW264.7细胞进行F-PBR06的细胞结合研究。在注射F-PBR06后1小时对载脂蛋白E(ApoE)小鼠和C57小鼠进行体内微型PET/CT成像。对主动脉组织进行CD68和F480免疫荧光染色。

结果

体外细胞研究显示RAW264.7细胞摄取F-PBR06。微型PET/CT成像成功识别了ApoE小鼠主动脉弓中的动脉粥样硬化病变,而在C57小鼠中未观察到信号。32周龄ApoE小鼠的斑块与肌肉比值显著高于22周龄ApoE小鼠,CD68免疫荧光染色和F480免疫荧光染色证实了这一点。

结论

TSPO放射性配体F-PBR06能够对富含巨噬细胞的动脉粥样硬化斑块进行无创PET/CT成像,并且在不同年龄小鼠中PET成像与斑块的体外免疫荧光染色之间呈正相关,从而代表了一种评估动脉粥样硬化斑块破裂易损性的潜在有吸引力的工具。

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