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Preclinical evaluation of [99mTc]Tc-labeled anti-EpCAM nanobody for EpCAM receptor expression imaging by immuno-SPECT/CT

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

Abstract

Purpose

Overexpression of epithelial cell adhesion molecule (EpCAM) plays essential roles in tumorigenesis and tumor progression in almost all epithelium-derived cancer. Monitoring EpCAM expression in tumors can be used for the diagnosis, staging, and prognosis of cancer patients, as well as guiding the individualized treatment of EpCAM-targeted drugs. In this study, we described the synthesis and evaluation of a site-specifically [99mTc]Tc-labeled EpCAM-targeted nanobody for the SPECT/CT imaging of EpCAM expression.

Methods

We first prepared the [99mTc]Tc-HYNIC-G4K; then, it was site-specifically connected to EpCAM-targeted nanobody NB4. The in vitro characteristics of [99mTc]Tc-NB4 were investigated in HT-29 (EpCAM positive) and HL-60 (EpCAM negative) cells, while the in vivo studies were performed using small-animal SPECT/CT in the subcutaneous tumor models and the lymph node metastasis model to verify the specific targeting capacity as well as the potential applications of [99mTc]Tc-NB4.

Results

[99mTc]Tc-NB4 displayed a high EpCAM specificity both in vitro and in vivo. SPECT/CT imaging revealed that [99mTc]Tc-NB4 was cleared rapidly from the blood and normal organs except for the kidneys, and HT-29 tumors were clearly visualized in contrast with HL-60 tumors. The uptake value of [99mTc]Tc-NB4 in HT-29 tumors was increased continuously from 3.77 ± 0.39%ID/g at 0.5 h to 5.53 ± 0.82%ID/g at 12 h after injection. Moreover, the [99mTc]Tc-NB4 SPECT/CT could clearly image tumor-draining lymph nodes.

Conclusion

[99mTc]Tc-NB4 is a broad-spectrum, specific, and sensitive SPECT radiotracer for the noninvasive imaging of EpCAM expression in the epithelium-derived cancer and revealed a great potential for the clinical translation.

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Funding

This research was supported by grants from the National Natural Science Foundation of China (NSFC) (projects 81871416, 81630045, 81927802, 81621063), the National Key R&D Program of China (2017YFA0205600).

Author information

Authors and Affiliations

  1. Medical Isotopes Research Center, Department of Radiation Medicine, School of Basic Medical Sciences, Peking University, Beijing, 100191, People’s Republic of China

    Tianyu Liu, Yue Wu, Linqing Shi, Liqiang Li, Biao Hu, Yanpu Wang, Hannan Gao, Xin Zhang, Huiyun Zhao, Bing Jia & Fan Wang

  2. State Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai, 201203, People’s Republic of China

    Xiaolu Yu

  3. Shanghai Novamab Biopharmaceuticals Co., Ltd, Shanghai, People’s Republic of China

    Yakun Wan

  4. Department of Integration of Chinese and Western Medicine, School of Basic Medical Sciences, Peking University, Beijing, 100191, People’s Republic of China

    Bing Jia

  5. Key Laboratory of Protein and Peptide Pharmaceuticals, CAS Center for Excellence in Biomacromolecules, Institute of Biophysics, Chinese Academy of Sciences, Beijing, 100101, People’s Republic of China

    Fan Wang

Authors
  1. Tianyu Liu
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  2. Yue Wu
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Correspondence to Bing Jia or Fan Wang.

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All applicable international, national, and/or institutional guidelines for the care and use of animals were followed. This article does not contain any studies with human participants performed by any of the authors.

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Liu, T., Wu, Y., Shi, L. et al. Preclinical evaluation of [99mTc]Tc-labeled anti-EpCAM nanobody for EpCAM receptor expression imaging by immuno-SPECT/CT. Eur J Nucl Med Mol Imaging 49, 1810–1821 (2022). https://doi.org/10.1007/s00259-021-05670-z

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