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Dynamic monitoring of active calcification in atherosclerosis by 18F–NaF PET imaging

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Abstract

The objective was to dynamically monitor the progression of atherosclerotic plaques in ApoE−/− mice with 18F–NaF PET imaging. The ApoE−/− mice were used to develop atherosclerosis models, and the C57BL/6 J mice were used as control. 18F–NaF PET was performed when the mice were 12, 20, and 30 weeks of age. Serum lipids and lipoproteins profiles, inflammatory cytokines, and calcification factors were tested by ELISA. The lipid distribution, morphology, and calcification of plaque were evaluated by Oil Red O, HE, and alizarin red staining. The correlation between imaging and the extent of calcification was analyzed by Pearson correlation analysis. The uptake of 18F–NaF in the aorta was gradually increased with each weekly extension. Compared with the ApoE−/− mice at the age of 12 weeks and 20 weeks, the levels of lipoprotein, inflammatory cytokines, and calcification factors were higher at 30 weeks. In Oil Red O, HE, and alizarin red staining, the extent of the lipid area and calcification increased with time. The correlation analysis showed that the uptake of 18F–NaF in the aorta was related to the extent of calcification. 18F–NaF may dynamically monitor the progression of atherosclerotic plaques and ongoing microcalcification formation.

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Abbreviations

PET:

Positron Emission Tomography

ELISA:

Enzyme-linked Immunosorbent Assay

TC:

Total Cholesterol

TG:

Total Triglyceride

HDL:

High Density Lipoprotein

LDL:

Low Density Lipoprotein

IL-1β:

Interleukin-1β

TNF-α:

Tumor Necrosis Factor-α

OCN:

Osteocalcin

BMP:

Bone Morphogenetic Protein

HE:

Hematoxylin–Eosin

CA:

Calcium Staining Area

TA:

Total Area

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Acknowledgements

This study was funded by the National Nature Science Foundation of China (81901796, 81671735, 81871407), and Shanghai Municipal Key Clinical Specialty (shslczdzk 03401), and the Scientific Research Foundation for Young Doctors of Zhongshan Hospital, Fudan University (2018ZSQN025). No potential conflicts of interest relevant to this article exist.

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Author notes

  1. Yan Hu and Pengcheng Hu have contributed equally to this paper.

Authors and Affiliations

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

    Yan Hu, Pengcheng Hu, Bingxin Hu, Weijia Chen, Dengfeng Cheng & Hongcheng Shi

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

    Yan Hu, Pengcheng Hu, Bingxin Hu, Weijia Chen, Dengfeng Cheng & Hongcheng Shi

Authors
  1. Yan Hu
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  2. Pengcheng Hu
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  3. Bingxin Hu
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  4. Weijia Chen
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  5. Dengfeng Cheng
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  6. Hongcheng Shi
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Contributions

YH and PCH participated in the experimental and data analysis. YH wrote the manuscript. BXH, and WJC dealt with the aortas. YH, DFC and HCS designed and controlled the quality of study. All authors were involved in the study and approved its final version.

Corresponding authors

Correspondence to Dengfeng Cheng or Hongcheng Shi.

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The authors declare that they have no conflict of interest.

Research using animal consents

The animal research protocol was approved by the medical ethics committee of Zhongshan Hospital, Fudan University. All experiments were performed following the relevant guidelines and regulations of Fudan University.

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Hu, Y., Hu, P., Hu, B. et al. Dynamic monitoring of active calcification in atherosclerosis by 18F–NaF PET imaging. Int J Cardiovasc Imaging 37, 731–739 (2021). https://doi.org/10.1007/s10554-020-02019-9

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  • DOI: https://doi.org/10.1007/s10554-020-02019-9

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