Predictive Value of [18F]ML-10 PET/CT in Early Response Evaluation of Combination Radiotherapy with Cetuximab on Nasopharyngeal Carcinoma
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Apoptosis may be an indication of success therapy, and precise detection of apoptosis can provide instructional suggestions in the therapy management of malignant tumors.
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.
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).
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.
Key wordsNasopharyngeal carcinoma Positron emission tomography CNE-1 cells Radiotherapy sensitivity Epidermal growth factor receptor
We wish to thank Jianmin Luo for excellent technical assistances.
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).
Compliance with Ethical Standards
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.
All applicable institutional and/or national guidelines for the care and use of animals were followed.
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