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Predictive Value of [18F]ML-10 PET/CT in Early Response Evaluation of Combination Radiotherapy with Cetuximab on Nasopharyngeal Carcinoma

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Abstract

Purpose

Apoptosis may be an indication of success therapy, and precise detection of apoptosis can provide instructional suggestions in the therapy management of malignant tumors.

Procedures

We used CNE-1 cell lines for in vitro experiments, and colony formation assay, CCK-8 assay, cell apoptosis analysis, and western blotting were performed. For in vivo experiments, subcutaneous xenotransplanted tumor models of CNE-1 in nude mice were established. Then, small animal positron emission tomography/X-ray computed tomography (PET/CT) images were acquired by tail intravenous injection of 2-(5-[18F]fluoropentyl)-2-methyl-malonic acid ([18F]ML-10) or 2-deoxy-2-[18F]fluoro-d-glucose ([18F]FDG) before and 24 h and 48 h after treatment. Moreover, expression of epidermal growth factor receptor (EGFR), Ki-67, Glut-1, and terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL) was examined by immunohistochemical examination. Tumor volumes of mice were recorded every 2 days.

Results

In the presence of Cetuximab, the number of colonies of CNE-1 cells decreased significantly after irradiation at 1 and 2 Gy. In addition, Cetuximab increased the radiation-induced cytotoxicity and apoptosis of CNE-1 cells. Mechanistic studies demonstrated that Cetuximab enhanced radiosensitivity by suppressing the EGFR/PI3-K/AKT pathway. In PET/CT imaging, the tumors showed clear uptake of [18F]ML-10 at 24 h and 48 h after combined treatment, and the value of tumor/muscle (T/M) and SUVmax (the max of standard uptake value) was significantly higher than those of the other three groups. The T/M of [18F]ML-10 uptake showed a positive correlation of 0.926 with the apoptosis index (P < 0.001). However, the uptake of [18F]FDG in tumors exhibited no trend among the four groups. The T/M of [18F]FDG revealed a positive correlation of 0.926 with Glut-1 intensity (P < 0.001).

Conclusions

Our work revealed that Cetuximab could increase the radiosensitivity of CNE-1 cells both in vitro and in vivo. Apoptosis imaging with [18F]ML-10 PET/CT is a promising modality for application in the response prediction of nasopharyngeal carcinoma.

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Acknowledgements

We wish to thank Jianmin Luo for excellent technical assistances.

Funding

This study was funded by the National Natural Science Foundation of China (No. 81501503) and the Shanghai Engineering Research Center of Molecular Imaging Probes Program (No. 14DZ2251400).

Author information

Author notes

  1. Bingxin Gu and Shuai Liu contributed equally to this work.

Authors and Affiliations

  1. Department of Nuclear Medicine, Fudan University Shanghai Cancer Center, No. 270, Dong’an Road, Xuhui District, Shanghai, China

    Bingxin Gu, Shuai Liu, Yuyun Sun, Jianping Zhang, Yongping Zhang, Xiaoping Xu, Huiyu Yuan, Mingwei Wang, Yingjian Zhang & Zhongyi Yang

  2. Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, China

    Bingxin Gu, Shuai Liu, Yuyun Sun, Jianping Zhang, Yongping Zhang, Xiaoping Xu, Huiyu Yuan, Mingwei Wang, Yingjian Zhang & Zhongyi Yang

  3. Center for Biomedical Imaging, Fudan University, Shanghai, China

    Bingxin Gu, Shuai Liu, Yuyun Sun, Jianping Zhang, Yongping Zhang, Xiaoping Xu, Huiyu Yuan, Mingwei Wang, Yingjian Zhang & Zhongyi Yang

  4. Shanghai Engineering Research Center of Molecular Imaging Probes, Shanghai, China

    Bingxin Gu, Shuai Liu, Yuyun Sun, Jianping Zhang, Yongping Zhang, Xiaoping Xu, Huiyu Yuan, Mingwei Wang, Yingjian Zhang & Zhongyi Yang

  5. Key Laboratory of Nuclear Physics and Ion-beam Application (MOE), Fudan University, Shanghai, China

    Bingxin Gu, Shuai Liu, Yuyun Sun, Jianping Zhang, Yongping Zhang, Xiaoping Xu, Huiyu Yuan, Mingwei Wang, Yingjian Zhang & Zhongyi Yang

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  1. Bingxin Gu
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  2. Shuai Liu
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Corresponding author

Correspondence to Zhongyi Yang.

Ethics declarations

All animal experiments met guidelines evaluated and approved by the ethics committee of Fudan University.

Conflict of Interest

The authors declare that they have no conflict of interest.

Ethical Approval

All applicable institutional and/or national guidelines for the care and use of animals were followed.

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Gu, B., Liu, S., Sun, Y. et al. Predictive Value of [18F]ML-10 PET/CT in Early Response Evaluation of Combination Radiotherapy with Cetuximab on Nasopharyngeal Carcinoma. Mol Imaging Biol 21, 538–548 (2019). https://doi.org/10.1007/s11307-018-1277-9

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  • DOI: https://doi.org/10.1007/s11307-018-1277-9

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