Xu Bing, Li Xiaowei, Yin Jipeng, Liang Cong, Liu Lijuan, Qiu Zhaoyan, Yao Liping, Nie Yongzhan, Wang Jing, Wu Kaichun
State Key Laboratory of Cancer Biology &Institute of Digestive Diseases, Xijing Hospital, The Fourth Military Medical University, Xi'an, China.
Department of Nuclear Medicine, Xijing Hospital, The Fourth Military Medical University, Xi'an, China.
Sci Rep. 2015 Mar 3;5:8626. doi: 10.1038/srep08626.
MG7-Ag, a specific gastric cancer-associated antigen, can be used to non-invasively monitor gastric cancer by molecular imaging with positron emission tomography/computed tomography (PET/CT). In this study, we prepared and evaluated a (68)Ga-labeled MG7 antibody as a molecular probe for nanoPET/CT imaging of gastric cancer in a BGC-823 tumor xenografted mouse model. Macrocyclic chelator 1,4,7-triazacyclononane-N,N0,N00-triacetic acid (NOTA)-conjugated MG7 antibody was synthesized and radiolabeled with (68)Ga (t1/2 = 67.71 min). Then, (68)Ga-NOTA-MG7 was tested using in vitro cytological studies, in vivo nanoPET/CT and Cerenkov imaging studies as well as ex vivo biodistribution and histology studies. The in vitro experiments demonstrated that (68)Ga-NOTA-MG7 has an excellent radiolabeling efficiency of approximately 99% without purification, and it is stable in serum after 120 min of incubation. Cell uptake and retention studies confirmed that (68)Ga-NOTA-MG7 has good binding affinity and tumor cell retention. For the nanoPET imaging study, the predominant uptake of (68)Ga-NOTA-MG7 was visualized in tumor, liver and kidneys. The tumor uptake reached at its peak (2.53 ± 0.28%ID/g) at 60 min pi. Cherenkov imaging also confirmed the specificity of tumor uptake. Moreover, the biodistribution results were consistent with the quantification data of nanoPET/CT imaging. Histologic analysis also demonstrated specific staining of BGC-823 tumor cell lines.
MG7抗原是一种特定的胃癌相关抗原,可通过正电子发射断层扫描/计算机断层扫描(PET/CT)分子成像用于无创监测胃癌。在本研究中,我们制备并评估了一种(68)Ga标记的MG7抗体,作为用于BGC-823肿瘤异种移植小鼠模型胃癌纳米PET/CT成像的分子探针。合成了大环螯合剂1,4,7-三氮杂环壬烷-N,N′,N″-三乙酸(NOTA)偶联的MG7抗体,并用(68)Ga(t1/2 = 67.71分钟)进行放射性标记。然后,通过体外细胞学研究、体内纳米PET/CT和切伦科夫成像研究以及体外生物分布和组织学研究对(68)Ga-NOTA-MG7进行测试。体外实验表明,(68)Ga-NOTA-MG7无需纯化即具有约99%的优异放射性标记效率,并且在孵育120分钟后在血清中稳定。细胞摄取和滞留研究证实,(68)Ga-NOTA-MG7具有良好的结合亲和力和肿瘤细胞滞留能力。对于纳米PET成像研究,(68)Ga-NOTA-MG7在肿瘤、肝脏和肾脏中可见主要摄取。在注射后60分钟时肿瘤摄取达到峰值(2.53±0.28%ID/g)。切伦科夫成像也证实了肿瘤摄取的特异性。此外,生物分布结果与纳米PET/CT成像的定量数据一致。组织学分析也显示了BGC-823肿瘤细胞系的特异性染色。