PMID- 30218389 OWN - NLM STAT- MEDLINE DCOM- 20200505 LR - 20200505 IS - 1860-2002 (Electronic) IS - 1536-1632 (Linking) VI - 21 IP - 3 DP - 2019 Jun TI - Predictive Value of [(18)F]ML-10 PET/CT in Early Response Evaluation of Combination Radiotherapy with Cetuximab on Nasopharyngeal Carcinoma. PG - 538-548 LID - 10.1007/s11307-018-1277-9 [doi] AB - 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-[(18)F]fluoropentyl)-2-methyl-malonic acid ([(18)F]ML-10) or 2-deoxy-2-[(18)F]fluoro-D-glucose ([(18)F]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 [(18)F]ML-10 at 24 h and 48 h after combined treatment, and the value of tumor/muscle (T/M) and SUV(max) (the max of standard uptake value) was significantly higher than those of the other three groups. The T/M of [(18)F]ML-10 uptake showed a positive correlation of 0.926 with the apoptosis index (P < 0.001). However, the uptake of [(18)F]FDG in tumors exhibited no trend among the four groups. The T/M of [(18)F]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 [(18)F]ML-10 PET/CT is a promising modality for application in the response prediction of nasopharyngeal carcinoma. FAU - Gu, Bingxin AU - Gu B AD - Department of Nuclear Medicine, Fudan University Shanghai Cancer Center, No. 270, Dong'an Road, Xuhui District, Shanghai, China. AD - Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, China. AD - Center for Biomedical Imaging, Fudan University, Shanghai, China. AD - Shanghai Engineering Research Center of Molecular Imaging Probes, Shanghai, China. AD - Key Laboratory of Nuclear Physics and Ion-beam Application (MOE), Fudan University, Shanghai, China. FAU - Liu, Shuai AU - Liu S AD - Department of Nuclear Medicine, Fudan University Shanghai Cancer Center, No. 270, Dong'an Road, Xuhui District, Shanghai, China. AD - Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, China. AD - Center for Biomedical Imaging, Fudan University, Shanghai, China. AD - Shanghai Engineering Research Center of Molecular Imaging Probes, Shanghai, China. AD - Key Laboratory of Nuclear Physics and Ion-beam Application (MOE), Fudan University, Shanghai, China. FAU - Sun, Yuyun AU - Sun Y AD - Department of Nuclear Medicine, Fudan University Shanghai Cancer Center, No. 270, Dong'an Road, Xuhui District, Shanghai, China. AD - Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, China. AD - Center for Biomedical Imaging, Fudan University, Shanghai, China. AD - Shanghai Engineering Research Center of Molecular Imaging Probes, Shanghai, China. AD - Key Laboratory of Nuclear Physics and Ion-beam Application (MOE), Fudan University, Shanghai, China. FAU - Zhang, Jianping AU - Zhang J AD - Department of Nuclear Medicine, Fudan University Shanghai Cancer Center, No. 270, Dong'an Road, Xuhui District, Shanghai, China. AD - Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, China. AD - Center for Biomedical Imaging, Fudan University, Shanghai, China. AD - Shanghai Engineering Research Center of Molecular Imaging Probes, Shanghai, China. AD - Key Laboratory of Nuclear Physics and Ion-beam Application (MOE), Fudan University, Shanghai, China. FAU - Zhang, Yongping AU - Zhang Y AD - Department of Nuclear Medicine, Fudan University Shanghai Cancer Center, No. 270, Dong'an Road, Xuhui District, Shanghai, China. AD - Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, China. AD - Center for Biomedical Imaging, Fudan University, Shanghai, China. AD - Shanghai Engineering Research Center of Molecular Imaging Probes, Shanghai, China. AD - Key Laboratory of Nuclear Physics and Ion-beam Application (MOE), Fudan University, Shanghai, China. FAU - Xu, Xiaoping AU - Xu X AD - Department of Nuclear Medicine, Fudan University Shanghai Cancer Center, No. 270, Dong'an Road, Xuhui District, Shanghai, China. AD - Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, China. AD - Center for Biomedical Imaging, Fudan University, Shanghai, China. AD - Shanghai Engineering Research Center of Molecular Imaging Probes, Shanghai, China. AD - Key Laboratory of Nuclear Physics and Ion-beam Application (MOE), Fudan University, Shanghai, China. FAU - Yuan, Huiyu AU - Yuan H AD - Department of Nuclear Medicine, Fudan University Shanghai Cancer Center, No. 270, Dong'an Road, Xuhui District, Shanghai, China. AD - Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, China. AD - Center for Biomedical Imaging, Fudan University, Shanghai, China. AD - Shanghai Engineering Research Center of Molecular Imaging Probes, Shanghai, China. AD - Key Laboratory of Nuclear Physics and Ion-beam Application (MOE), Fudan University, Shanghai, China. FAU - Wang, Mingwei AU - Wang M AD - Department of Nuclear Medicine, Fudan University Shanghai Cancer Center, No. 270, Dong'an Road, Xuhui District, Shanghai, China. AD - Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, China. AD - Center for Biomedical Imaging, Fudan University, Shanghai, China. AD - Shanghai Engineering Research Center of Molecular Imaging Probes, Shanghai, China. AD - Key Laboratory of Nuclear Physics and Ion-beam Application (MOE), Fudan University, Shanghai, China. FAU - Zhang, Yingjian AU - Zhang Y AD - Department of Nuclear Medicine, Fudan University Shanghai Cancer Center, No. 270, Dong'an Road, Xuhui District, Shanghai, China. AD - Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, China. AD - Center for Biomedical Imaging, Fudan University, Shanghai, China. AD - Shanghai Engineering Research Center of Molecular Imaging Probes, Shanghai, China. AD - Key Laboratory of Nuclear Physics and Ion-beam Application (MOE), Fudan University, Shanghai, China. FAU - Yang, Zhongyi AU - Yang Z AD - Department of Nuclear Medicine, Fudan University Shanghai Cancer Center, No. 270, Dong'an Road, Xuhui District, Shanghai, China. yangzhongyi21@163.com. AD - Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, China. yangzhongyi21@163.com. AD - Center for Biomedical Imaging, Fudan University, Shanghai, China. yangzhongyi21@163.com. AD - Shanghai Engineering Research Center of Molecular Imaging Probes, Shanghai, China. yangzhongyi21@163.com. AD - Key Laboratory of Nuclear Physics and Ion-beam Application (MOE), Fudan University, Shanghai, China. yangzhongyi21@163.com. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't PL - United States TA - Mol Imaging Biol JT - Molecular imaging and biology JID - 101125610 RN - 0 (5-fluoropentyl-2-methylmalonic acid) RN - 0 (Glucose Transporter Type 1) RN - 0Z5B2CJX4D (Fluorodeoxyglucose F18) RN - 8LL8S712J7 (Methylmalonic Acid) RN - EC 2.7.10.1 (ErbB Receptors) RN - EC 2.7.11.1 (Proto-Oncogene Proteins c-akt) RN - PQX0D8J21J (Cetuximab) SB - IM MH - Animals MH - Cell Death/drug effects MH - Cell Line, Tumor MH - Cell Proliferation/drug effects MH - Cetuximab/pharmacology/*therapeutic use MH - Combined Modality Therapy MH - ErbB Receptors/metabolism MH - Female MH - Fluorodeoxyglucose F18/metabolism MH - Glucose Transporter Type 1/metabolism MH - Humans MH - Methylmalonic Acid/analogs & derivatives/chemistry MH - Mice, Inbred BALB C MH - Mice, Nude MH - Nasopharyngeal Carcinoma/diagnostic imaging/*drug therapy/pathology/*radiotherapy MH - Phosphatidylinositol 3-Kinases/metabolism MH - *Positron Emission Tomography Computed Tomography MH - Predictive Value of Tests MH - Proto-Oncogene Proteins c-akt/metabolism MH - Signal Transduction/drug effects MH - Tumor Stem Cell Assay OTO - NOTNLM OT - CNE-1 cells OT - Epidermal growth factor receptor OT - Nasopharyngeal carcinoma OT - Positron emission tomography OT - Radiotherapy sensitivity EDAT- 2018/09/16 06:00 MHDA- 2020/05/06 06:00 CRDT- 2018/09/16 06:00 PHST- 2018/09/16 06:00 [pubmed] PHST- 2020/05/06 06:00 [medline] PHST- 2018/09/16 06:00 [entrez] AID - 10.1007/s11307-018-1277-9 [pii] AID - 10.1007/s11307-018-1277-9 [doi] PST - ppublish SO - Mol Imaging Biol. 2019 Jun;21(3):538-548. doi: 10.1007/s11307-018-1277-9.