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Integrin α6-Targeted Magnetic Resonance Imaging of Hepatocellular Carcinoma in Mice

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Abstract

Purpose

Magnetic resonance imaging (MRI) has a high spatial resolution for detecting hepatocellular carcinoma (HCC). Integrin α6 has emerged as a diagnostic and prognostic biomarker of HCC. Here, we developed the MR contrast agent RWY-dL-(Gd-DOTA)4 based on the integrin α6-targeted RWY peptide that we previously identified to detect HCC.

Procedures

Contrast-enhanced MRI was carried out to evaluate the use of RWY-dL-(Gd-DOTA)4 to detect HCC lesions in subcutaneous and diethylnitrosamine (DEN)-induced HCC mouse models.

Results

Enhancement MR signals were observed in HCC-LM3 subcutaneous liver tumors in the first 5 min post-injection of RWY-dL-(Gd-DOTA)4 at a low dose of 0.03 mmol Gd/kg. Moreover, RWY-dL-(Gd-DOTA)4 generated superior contrast enhancement for liver tumors in chemical-induced HCC mice. Importantly, RWY-dL-(Gd-DOTA)4 provided complementary enhancement MR signals to the clinical available hepatobiliary MR contrast agent gadoxetate disodium Gd-EOB-DTPA. Additionally, RWY-dL-(Gd-DOTA)4 showed minimal gadolinium retention in normal tissues and organs at 48 h post-injection.

Conclusion

These findings potentiate the use of RWY-dL-(Gd-DOTA)4 for the MRI of HCC to improve the diagnosis of HCC.

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Acknowledgments

The authors thank Yong-Jian Peng and Cheng Li for their helpful technical assistance.

Funding

This work was supported by grants from the National Natural Science Foundation of China (NSFC) (projects 81602364, 81671965, 81621004, 81520108022, 81572403), Science & Technology Project of Guangdong Province (2017A020211010 and 2014B020210002), the National Key R&D Program of China (2017YFA0505600 and 2016YFA0502100), Health & Medical Collaborative Innovation Project of Guangzhou City, China (201400000001 and 20150802024), and Sci-Tech Project Foundation of Guangzhou City (201607020038). The raw data used in this article has been uploaded onto the Research Data Deposit public platform (www.researchdata.org.cn), with the approval number as RDDB2019000667.

Author information

Author notes

  1. Yun Zhang, Jing Zhao and Jing Cai contributed equally to this work.

Authors and Affiliations

  1. Guangdong Provincial Key Laboratory of Proteomics, State Key Laboratory of Organ Failure Research, Department of Pathophysiology, School of Basic Medical Science, Southern Medical University, No.1023 Shatai South Road, Guangzhou, 510515, Guangdong Province, China

    Yun Zhang & Yong Jiang

  2. State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Sun Yat-sen University Cancer Center/Cancer Hospital, 651 Dongfeng East Road, Guangzhou, 510060, China

    Jing Zhao, Jing Cai, Jia-Cong Ye, Yi-Tai Xiao, Yan Mei, Mu-Sheng Zeng, Chuan-Miao Xie & Guo-Kai Feng

  3. Department of Medical Imaging, State Key Laboratory of Oncology in South China, Sun Yat-sen University Cancer Center/Cancer Hospital, 651 Dongfeng East Road, Guangzhou, 510060, China

    Chuan-Miao Xie

Authors
  1. Yun Zhang
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  2. Jing Zhao
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  3. Jing Cai
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  9. Yong Jiang
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  10. Guo-Kai Feng
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Corresponding authors

Correspondence to Chuan-Miao Xie, Yong Jiang or Guo-Kai Feng.

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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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Zhang, Y., Zhao, J., Cai, J. et al. Integrin α6-Targeted Magnetic Resonance Imaging of Hepatocellular Carcinoma in Mice. Mol Imaging Biol 22, 864–872 (2020). https://doi.org/10.1007/s11307-019-01437-z

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