Abstract
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Purpose: The aim of this study was to explore the 18 kDa translocator protein (TSPO) radioligand [18F]N-fluoroacetyl-N-(2,5-dimethoxybenzyl)-2-phenoxyaniline (18F-PBR06) as a positron emission tomography (PET) imaging biomarker to be used to image inflammation in atheroclerosis (AS) and evaluate the vulnerability to repture of atherosclerotic plaques.
Methods: RAW264.7 cells were used for cell analysis of 18F-PBR06. The ApoE-knockout (ApoE-/-) mice fed a Western diet were selected to establish animal models, with C57BL/6J mice used for control. After the feeding at 22 weeks and 32 weeks, In vivo PET/CT imaging for ApoE-/- mice and C57BL/6J mice was performed at 1h after injection of 18F-PBR06. CD68+ and FH480 immunohistochemistry staining were performed in the aorta tissues.Results: In vitro cell studies showed specific binding of the tracer to RAW264.7 macrophage cells. PET imaging successfully identified the atherosclerotic lesions in the aortic arch of ApoE-/- mice, while background signal was observed in the control groups. The value of plaque-to-muscle (P/M) in each part of the aorta of ApoE-/- mice was higher than the C57BL/6J mice. The P/M in 32W (Fig.2) were significantly higher than that in 22W (Fig.1). Which was confirmed by CD68+ and FH480 immunohistochemistry staining.Conclusion: The TSPO radioligand 18F-PBR06, allows non-invasive PET/CT imaging diagnosis and assessment of macrophage expression in atherosclerotic plaques. Furthermore, this probe may be used as a new molecular imaging agent represent an attractive tool for diagnosing vulnerable atherosclerotic plaques in patients. Keywords: PET ; [18F]-PBR06; plaques; macrophage;Figure1. (A)&(B) 18F-PBR06 PET/CT imaging of APOE-/- mice on 22W after gene knockout. White circle indicate the region of high uptake in the thoracic aorta. ©&(D) 18F-PBR06 PET/CT imaging of C57 mice on 22W. € Quantification of 18F-PBR06 in plaques and muscles in APOE-/- and C57 mice on 22W. (F) The ratio of P/M in APOE-/- and C57 mice on 22W. Figure 2. (A)&(B) 18F-PBR06 PET/CT imaging of APOE-/- mice on 32W after gene knockout. White circle indicate the region of high uptake in the thoracic aorta. ©&(D) 18F-PBR06 PET/CT imaging of C57 mice on 32W. € Quantification of 18F-PBR06 in plaques and muscles in APOE-/- and C57 mice on 32W. (F) The ratio of P/M in APOE-/- andC57 mice on 32W.
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