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EDB-FN targeted probes for the surgical navigation, radionuclide imaging, and therapy of thyroid cancer

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

Abstract

Purpose

Extradomain B of fibronectin (EDB-FN) is a promising diagnostic and therapeutic biomarker for thyroid cancer (TC). Here, we identified a high-affinity EDB-FN targeted peptide named EDBp (AVRTSAD) and developed three EDBp-based probes, Cy5-PEG4-EDBp(Cy5-EDBp), [18F]-NOTA-PEG4-EDBp([18F]-EDBp), and [177Lu]-DOTA-PEG4-EDBp ([177Lu]-EDBp), for the surgical navigation, radionuclide imaging, and therapy of TC.

Methods

Based on the previously identified EDB-FN targeted peptide ZD2, the optimized EDB-FN targeted peptide EDBp was identified by using the alanine scan strategy. Three EDBp-based probes, Cy5-EDBp, [18F]-EDBp, and [177Lu]-EDBp, were developed for fluorescence imaging, positron emission tomography (PET) imaging, and radiotherapy in TC tumor-bearing mice, respectively. Additionally, [18F]-EDBp was evaluated in two TC patients.

Results

The binding affinity of EDBp to the EDB fragment protein (Kd = 14.4 ± 1.4 nM, n = 3) was approximately 336-fold greater than that of the ZD2 (Kd = 4839.7 ± 361.7 nM, n = 3). Fluorescence imaging with Cy5-EDBp facilitated the complete removal of TC tumors. [18F]-EDBp PET imaging clearly delineated TC tumors, with high tumor uptake (16.43 ± 1.008%ID/g, n = 6, at 1-h postinjection). Radiotherapy with [177Lu]-EDBp inhibited tumor growth and prolonged survival in TC tumor-bearing mice (survival time of different treatment groups: saline vs. EDBp vs. ABRAXANE vs. [177Lu]-EDBp = 8.00 d vs. 8.00 d vs. 11.67 d vs. 22.33 d, ***p < 0.001). Importantly, the first-in-human evaluation of [18F]-EDBp demonstrated that it had specific targeting properties (SUVmax value of 3.6) and safety.

Conclusion

Cy5-EDBp, [18F]-EDBp, and [177Lu]-EDBp are promising candidates for the surgical navigation, radionuclide imaging, and radionuclide therapy of TC, respectively.

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Data availability

The datasets generated during and/or analyzed during the current study are available in the research database of SYSCC.

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Funding

This work was supported by grants from Natural Science Foundation of China (81972531), Fundamental Research Funds for the Central Universities (19ykpy174).

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Author notes

  1. Chunjing Yu, Guokai Feng, Wei Fan, Ruping Li, Huihui He, Xinling Li And Xiaobin Zheng contributed equally.

Authors and Affiliations

  1. State Key Laboratory of Oncology in South China, Sun Yat-Sen University Cancer Center, Guangzhou , 510060, Guangdong, People’s Republic of China

    Ruping Li, Xinling Li, Xiaobin Zheng, Zhijian Li, Hu Zhang, Jiacong Ye, Weiguang Zhang, Guokai Feng & Wei Fan

  2. Department of Nuclear Medicine, Affiliated Hospital of Jiangnan University, Wuxi, 214000, China

    Huihui He & Chunjing Yu

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  1. Ruping Li
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Contributions

Study concept and design, WF, GF, and CY; acquisition of data, RL, HH, XL, XZ, ZL, HZ, and WZ; analysis and interpretation of data, RL; drafting of the manuscript, RL, GKF, and JY; critical revision of the manuscript for important intellectual content, GKF and WF; obtained funding, GKF and WF; administrative, technical, or material support, XL, ZL, HZ, JY, KF, and WF; and study supervision, WF, GKF, and CY.

Corresponding authors

Correspondence to Chunjing Yu, Guokai Feng or Wei Fan.

Ethics declarations

Ethics approval

The study has been approved by the institutional review board of Sun Yat-sen Cancer Center (SYSCC) and Affiliated Hospital of Jiangnan University (ethical code: LS2023011). All animal experiments were approved by the Institutional Animal Care and Use Committee at SYSCC (ethical code: L102012021080H). And the experiment of human tissues was approved by Ethics Committee of SYSCC (ethical code: B2022-434–01).

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The authors declare no competing interests.

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Li, R., He, H., Li, X. et al. EDB-FN targeted probes for the surgical navigation, radionuclide imaging, and therapy of thyroid cancer. Eur J Nucl Med Mol Imaging 50, 2100–2113 (2023). https://doi.org/10.1007/s00259-023-06147-x

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