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68Ga标记的MG7抗体评估:一种用于胃癌PET/CT成像的靶向探针。

Evaluation of 68Ga-labeled MG7 antibody: a targeted probe for PET/CT imaging of gastric cancer.

作者信息

Xu Bing, Li Xiaowei, Yin Jipeng, Liang Cong, Liu Lijuan, Qiu Zhaoyan, Yao Liping, Nie Yongzhan, Wang Jing, Wu Kaichun

机构信息

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.

出版信息

Sci Rep. 2015 Mar 3;5:8626. doi: 10.1038/srep08626.

Abstract

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.

摘要

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。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/229b/4346831/98f132eeadb1/srep08626-f1.jpg

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