Shi Dai, Cao Qinghui, Zhang Yingying, Cheng Yuan, Xu Zhan, Cheng Dengfeng, Shi Hongcheng
Abstract
ObjectiveTo screen 89Zr-labeled anti-epidermal growth factor receptor (EGFR) and human epidermal growth factor receptor 2 (HER2) monoclonal antibody molecular probes suitable for monitoring the gastric mucinous adenocarcinoma bearing mouse models with low glucose metabolism.
MethodsThe expression of EGFR and HER2 in the MGC803 gastric cancer cell line was verified by analyzing cell slides and xenograft tumor sections. 89Zr-Deferoxamine (DFO)-Cetuximab and 89Zr-DFO-Pertuzumab were prepared and the radiochemical purity was detected. Cell binding experiments and blocking experiments were performed to verify the binding ability and specificity of the probes. Twelve gastric mucinous adenocarcinoma bearing mouse models were divided into 3 groups (n=4 in each group): 89Zr-DFO-Cetuximab group (7.4 MBq/mouse, 74 μg/mouse), 89Zr-DFO-Pertuzumab group (7.4 MBq/mouse, 70 μg/mouse) and 18F-fluorodeoxyglucose (FDG) group (7.4 MBq/mouse). MicroPET imaging was performed at 4, 24 and 48 h (18F-FDG group underwent imaging at 1 h only) post-injection. The biodistribution study of 89Zr-DFO-Cetuximab and 89Zr-DFO-Pertuzumab was conducted in 2 groups (n=4 in each group) 48 h after the injection. The independent sample t test was used for data analysis.
ResultsThe immunofluorescent staining demonstrated EGFR expression was significantly higher than HER2 expression in MGC803 gastric cancer cell line. The radiochemical purity of 89Zr-DFO-Cetuximab and 89Zr-DFO-Pertuzumab were both more than 95%, and the specific activities were 100 and 95 MBq/mg, respectively. The two probes had good stability in normal saline and fetal bovine serum, with the radiochemical purity higher than 80% at 72 h. MicroPET imaging showed that the uptake of 89Zr-DFO-Cetuximab in the MGC803 tumor was significantly higher than that of 18F-FDG and 89Zr-DFO-Pertuzumab. The biodistribution study demonstrated the 89Zr-DFO-Cetuximab uptake (percentage activity of injection dose per gram of tissue, %ID/g) of tumors at 48 h was significantly higher than that of 89Zr-DFO-Pertuzumab (56.3±12.0 vs 22.0±3.6; t=4.31, P<0.05).
ConclusionCompared with 89Zr-DFO-Pertuzumab, 89Zr-DFO-Cetuximab has a better potential for non-invasive monitoring of gastric mucinous adenocarcinoma with low glucose metabolism.
Key words:
Adenocarcinoma, mucinous; Stomach; Receptor, epidermal growth factor; Isotope labeling; Zirconium; Positron-emission tomography; Tumor cells, cultured; Mice, nude
Contributor Information
Shi Dai
Shanghai Institute of Medical Imaging
Department of Nuclear Medicine, Zhongshan Hospital, Fudan University
Nuclear Medicine Institute of Fudan University
Cancer Center, Zhongshan Hospital, Fudan University, Shanghai 200032, China
Cao Qinghui
Department of Pharmacy, Zhongshan Hospital, Fudan University, Shanghai 200032, China
Zhang Yingying
Shanghai Institute of Medical Imaging
Department of Nuclear Medicine, Zhongshan Hospital, Fudan University
Nuclear Medicine Institute of Fudan University
Cancer Center, Zhongshan Hospital, Fudan University, Shanghai 200032, China
Cheng Yuan
Shanghai Institute of Medical Imaging
Department of Nuclear Medicine, Zhongshan Hospital, Fudan University
Nuclear Medicine Institute of Fudan University
Cancer Center, Zhongshan Hospital, Fudan University, Shanghai 200032, China
Xu Zhan
Shanghai Institute of Medical Imaging
Department of Nuclear Medicine, Zhongshan Hospital, Fudan University
Nuclear Medicine Institute of Fudan University
Cancer Center, Zhongshan Hospital, Fudan University, Shanghai 200032, China
Cheng Dengfeng
Shanghai Institute of Medical Imaging
Department of Nuclear Medicine, Zhongshan Hospital, Fudan University
Nuclear Medicine Institute of Fudan University
Cancer Center, Zhongshan Hospital, Fudan University, Shanghai 200032, China
Shi Hongcheng
Shanghai Institute of Medical Imaging
Department of Nuclear Medicine, Zhongshan Hospital, Fudan University
Nuclear Medicine Institute of Fudan University
Cancer Center, Zhongshan Hospital, Fudan University, Shanghai 200032, China
