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Transferrin receptor 1 targeted optical imaging for identifying glioma margin in mouse models

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Journal of Neuro-Oncology Aims and scope Submit manuscript

Abstract

Objective

Optical molecular imaging technology that indiscriminately detects intracranial glioblastoma (GBM) can help neurosurgeons effectively remove tumor masses. Transferrin receptor 1 (TfR 1) is a diagnostic and therapeutic target in GBM. A TfR 1-targeted peptide, CRTIGPSVC (CRT), was shown to cross the blood brain barrier (BBB) and accumulate at high levels in GBM tissues. In this study, we synthesized a TfR 1-targeted near-infrared fluorescent (NIRF) probe, Cy5-CRT, for identifying the GBM tissue margin in mouse models.

Methods

We initially confirmed the overexpression of TfR 1 in GBM and the tumor-specific homing ability of Cy5-CRT in subcutaneous and orthotopic GBM mouse models. We then examined the feasibility of Cy5-CRT for identifying the tumor margin in orthotopic GBM xenografts. Finally, we compared Cy5-CRT with the clinically used fluorescein sodium in identifying tumor margins.

Results

Cy5-CRT specifically accumulated in GBM tissues and detected the tumor burden with exceptional contrast in mice with orthotopic GBM, enabling fluorescence-guided GBM resection under NIRF live imaging conditions. Importantly, Cy5-CRT recognized the GBM tissue margin more clearly than fluorescein sodium.

Conclusions

The TfR 1-targeted optical probe Cy5-CRT specifically differentiates tumor tissues from the surrounding normal brain with high sensitivity, indicating its potential application for the precise surgical removal of GBM.

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Acknowledgements

The authors thank Jia-Cong Ye and Yi-Tai Xiao for their technical support.

Funding

This study was supported by grants from the National Basic Research Program (973, 2015CB755505), the National Natural Science Foundation of China (NSFC) (81372685, 81872059, 81572479 and 81772677), Guangzhou Science Technology and Innovation Project (201508020125), the Science and Technology Planning Project (2016A020213004) and the Natural Science Foundation of Guangdong Province (NSFG) (2016A030313309).

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Author notes

  1. Xiang-Rong Ni, Yi-Ying Zhao, Hai-Ping Cai have contributed equally to this work.

Authors and Affiliations

  1. Department of Neurosurgery/Neuro-Oncology, Sun Yat-Sen University Cancer Center, Guangzhou, China

    Xiang-Rong Ni, Hai-Ping Cai, Zhi-Hui Yu, Jing Wang, Fu-Rong Chen, Yan-Jiao Yu, Guo-Kai Feng & Zhong-Ping Chen

  2. State Key Laboratory of Oncology in South China, Guangzhou, China

    Xiang-Rong Ni, Hai-Ping Cai, Zhi-Hui Yu, Jing Wang, Fu-Rong Chen & Yan-Jiao Yu

  3. Collaborative Innovation Center for Cancer Medicine, Guangzhou, China

    Xiang-Rong Ni, Hai-Ping Cai, Zhi-Hui Yu, Jing Wang, Fu-Rong Chen & Yan-Jiao Yu

  4. Department of Neurosurgery, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, Guangzhou, 510235, China

    Yi-Ying Zhao

  5. Department of Neurosurgery/Neuro-Oncology, Principal Investigator, State Key Laboratory of Oncology in South China, Sun Yat-Sen University Cancer Center/Cancer Hospital, 651 Dongfeng Rd East, Guangzhou, 510060, China

    Guo-Kai Feng & Zhong-Ping Chen

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Correspondence to Guo-Kai Feng or Zhong-Ping Chen.

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Ni, XR., Zhao, YY., Cai, HP. et al. Transferrin receptor 1 targeted optical imaging for identifying glioma margin in mouse models. J Neurooncol 148, 245–258 (2020). https://doi.org/10.1007/s11060-020-03527-3

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