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Sodium Pump Na + /K + ATPase Subunit α1-Targeted Positron Emission Tomography Imaging of Hepatocellular Carcinoma in Mouse Models

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Abstract

Purpose

Positron emission tomography (PET) imaging was not efficiently used in the early diagnosis of hepatocellular carcinoma (HCC) due to the lack of appropriate tracers. Sodium pump Na + /K + ATPase subunit α1 (NKAα1) emerges to be a potential diagnostic biomarker of HCC. Here, we investigated the feasibility of 18F-ALF-NOTA-S3, a PET tracer based on an NKAα1 peptide, to detect small HCC.

Procedures

GEPIA database was searched to obtain the expression characteristics of NKAα1 in HCC and its relationship with the prognosis. PET/CT was performed in orthotopic, diethylnitrosamine (DEN)-induced and genetically engineered HCC mouse models to evaluate the use of 18F-ALF-NOTA-S3 to detect HCC lesions.

Results

NKAα1 is overexpressed in early HCC with a high positive rate and may correlate with poor survival. In orthotopic, DEN-induced and genetically engineered HCC mouse models, PET/CT imaging showed a high accumulation of 18F-ALF-NOTA-S3 in the tumor. The tumor-to-liver ratios are 2.56 ± 1.02, 4.41 ± 1.09, and 4.59 ± 0.65, respectively. Upregulated NKAα1 expression in tumors were verified by immunohistochemistry. Furthermore, 18F-ALF-NOTA-S3 has the ability to detect small HCC lesions with diameters of 2–5 mm.

Conclusions

NKAα1 may serve as a suitable diagnostic biomarker for HCC. 18F-ALF-NOTA-S3 shows great potential for PET imaging of HCC.

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Funding

This work was supported by the National Natural Science Foundation of China (NSFC) (projects 81972531 and 82001855), the China Postdoctoral Science Foundation (2019M663297), and the Fundamental Research Funds for the Central Universities 19ykpy174.

Author information

Author notes

  1. Si Tang and XiaoChun Yang contributed equally to this work and are co-first authors.

Authors and Affiliations

  1. State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Sun Yat-Sen University Cancer Center, Guangzhou, 510060, China

    Si Tang, XiaoChun Yang, Chao Zhou, Yan Mei, JiaCong Ye, XiaoFei Zhang, GuoKai Feng, WeiGuang Zhang, Xu Zhang & Wei Fan

  2. Department of Nuclear Medicine, Sun Yat-Sen University Cancer Center, Guangzhou, 510060, China

    Si Tang, XiaoChun Yang, Chao Zhou, XiaoFei Zhang, WeiGuang Zhang, Xu Zhang & Wei Fan

Authors
  1. Si Tang
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  4. Yan Mei
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Contributions

All authors contributed to the study conception and design. Material preparation, data collection, and analysis were performed by ST, XCY, and YM. ST, JCY, XFZ, and GKF performed the experiments. The whole experiment was completed under the guidance of WGZ, XZ, and WF. The first draft of the manuscript was written by ST and XCY. All authors commented on the previous versions of the manuscript and approved the final manuscript.

Corresponding authors

Correspondence to WeiGuang Zhang, Xu Zhang or Wei Fan.

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Ethics Approval and Consent to Participate

All animal studies were approved by the Animal Care at Sun Yat-sen University Cancer Center and in accordance with its guidelines.

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The authors declare that they have no conflict of interest.

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Tang, S., Yang, X., Zhou, C. et al. Sodium Pump Na + /K + ATPase Subunit α1-Targeted Positron Emission Tomography Imaging of Hepatocellular Carcinoma in Mouse Models. Mol Imaging Biol 24, 384–393 (2022). https://doi.org/10.1007/s11307-021-01659-0

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  • DOI: https://doi.org/10.1007/s11307-021-01659-0

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