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P2X7 receptor-specific radioligand 18F-FTTM for atherosclerotic plaque PET imaging

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European Journal of Nuclear Medicine and Molecular Imaging Aims and scope Submit manuscript

Abstract

Purpose

P2X7 receptors have been considered as a promising biomarker for vulnerable atherosclerotic plaques, which are highly expressed by that instability-associated factors such as macrophages. Thus, we aim to investigate the feasibility of using specific P2X7-targeted 18F-labeled tracer 18F-FTTM ((2-chloro-3-[18F]fluorophenyl)[1,4,6,7-tetrahydro-1-(2-pyrimidinyl)-5H-1,2,3-triazolo[4,5-c]pyridin-5-yl]methanone) for PET study of vulnerable atherosclerotic plaques identification.

Method

The radioligand 18F-FTTM was achieved based on the copper-mediated radiofluorination of arylstannane. In vitro and in vivo experiments were performed to verify the biochemical properties. Dynamic 18F-FTTM Micro-PET/CT imaging was performed for 1 h on ApoE−/− mice (10, 20, 30 weeks on high-fat diet) and wild-type C57BL/6 J mice on normal diet. Ex vivo PET imaging was conducted to verify the specificity of the radioligand. Serum inflammatory cytokines, lipids, and lipoproteins profiles were detected by ELISA. The lipid distribution and morphology of plaques were evaluated by Oil Red O, HE, Masson, and immunofluorescence stainings.

Results

18F-FTTM was afforded with decay-corrected radiochemical yields of 5–10%, specific activity of 269–320 MBq/nmol (n = 8, EOS), and radiochemical purity of above 99%. 18F-FTTM showed excellent stability in vitro, rapid blood clearance in mice, good affinity to RAW264.7 cells. We observed an increase in both in vivo and ex vivo imagings as disease progressed, and the imaging signatures correlated with histopathological features. Furthermore, compared with 18F-FDG imaging, the SUVmax values of 18F-FTTM at the aortic arch of ApoE−/− mice of high-fat feeding for 20 and 30 weeks were 43% and 53% higher than those of the control group, respectively.

Conclusion

We innovatively apply a new type P2X7-targeted PET probe (18F-FTTM) to identify vulnerable atherosclerotic plaques, to detect the inflammatory response of atherosclerosis, and to provide a powerful non-invasive method for the diagnosis of atherosclerotic lesions and new drug screening for accurate treatment.

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Funding

This study was funded by the National Nature Science Foundation of China (No.81471706, 11875114, 81871407, China), Shanghai Municipal Science and Technology Committee of Shanghai outstanding academic leaders plan (No.21XD1423500, China), Shanghai Municipal Key Clinical Specialty Project (SHSLCZDZK03401, China) and Clinical Research Project of Zhongshan Hospital(No.2020ZSLC20, China).

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Author notes

  1. Zhequan Fu and Qingyu Lin contributed equally.

Authors and Affiliations

  1. Department of Nuclear Medicine, Zhongshan Hospital, Fudan University, 180 Fenglin Rd, Shanghai, 200032, China

    Zhequan Fu, Qingyu Lin, Zhan Xu, Yanzhao Zhao, Yuan Cheng, Dai Shi, Wenhui Fu, Tingting Yang, Hongcheng Shi & Dengfeng Cheng

  2. Institute of Nuclear Medicine, Fudan University, Shanghai, 200032, China

    Zhequan Fu, Qingyu Lin, Zhan Xu, Yanzhao Zhao, Yuan Cheng, Dai Shi, Wenhui Fu, Tingting Yang, Hongcheng Shi & Dengfeng Cheng

  3. Shanghai Institute of Medical Imaging, Shanghai, 200032, China

    Zhequan Fu, Qingyu Lin, Zhan Xu, Yanzhao Zhao, Yuan Cheng, Dai Shi, Wenhui Fu, Tingting Yang, Hongcheng Shi & Dengfeng Cheng

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  1. Zhequan Fu
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  2. Qingyu Lin
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Corresponding authors

Correspondence to Hongcheng Shi or Dengfeng Cheng.

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All applicable international, national, and/or institutional guidelines for the care and use of animals were followed. Animal care and experimental procedures were conducted in compliance with the Helsinki Declaration and approved by the Ethical Committee of Zhongshan Hospital, Fudan University.

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Fu, Z., Lin, Q., Xu, Z. et al. P2X7 receptor-specific radioligand 18F-FTTM for atherosclerotic plaque PET imaging. Eur J Nucl Med Mol Imaging 49, 2595–2604 (2022). https://doi.org/10.1007/s00259-022-05689-w

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  • DOI: https://doi.org/10.1007/s00259-022-05689-w

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