The uptake exploration of 68Ga-labeled NGR in well-differentiated hepatocellular carcinoma xenografts: Indication for the new clinical translational of a tracer based on NGR
The uptake exploration of 68Ga-labeled NGR in well-differentiated hepatocellular carcinoma xenografts: Indication for the new clinical translational of a tracer based on NGR
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68Ga标记的NGR在高分化肝细胞癌异种移植物中的摄取探索：基于NGR的示踪剂新的临床转化的指示。
DOI：
10.3892/or.2017.5933
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发表时间：
2017-11-01
期刊：
影响因子：
4.2
通讯作者：
Wang, Jing
中科院分区：
文献类型：
--
作者：
Gao, Yongheng;Wang, Zhengjie;Wang, Jing
18F-FDG在肝细胞癌（HCC）中的摄取率低，诊断效率低，特别是在分化良好的HCC中。NGR肽选择性靶向CD 13，其在许多类型的肿瘤细胞以及新生血管细胞中过表达。在本研究中，我们的目的是评估利用68 Ga-NGR成像CD 13阳性分化良好的HCC异种移植物的可行性。在基于SMMC-7721的高分化HCC异种移植物中定量比较了68 Ga-NGR和18F-FDG的体外细胞摄取、体内micro-PET/CT成像和生物分布研究。人纤维肉瘤（HT-1080）和人结肠直肠腺癌（HT-29）异种移植物分别用作CD 13的阳性和阴性参考组。通过免疫荧光染色和免疫荧光染色研究定性验证CD 13的表达。免疫印迹法半定量分析CD 13和葡萄糖-6-磷酸酶（G6 β）的表达水平。SMMC-7721细胞对68 Ga ‑NGR的摄取显著高于18F-FDG（1.23± 0.11vs.0.515 ±0.14%; P<0.01）。体内micro-PET/CT成像结果显示，SMMC-7721来源的肿瘤中68 Ga-NGR的摄取为2.17±0.21% ID/g（每克组织的注射剂量百分比），高于18F-FDG（0.73±0.26% ID/g; P<0.01）;然而，68 Ga-NGR的肿瘤/肝脏比是18F-FDG的2倍。我们的结论是，在高分化HCC异种移植物中，68 Ga-NGR的摄取在体外和体内均显著高于18F-FDG，因此，它有希望在高分化HCC PET/CT诊断中进一步临床转化。
18F-FDG has low uptake and poor diagnostic efficiency in hepatocellular carcinoma (HCC), particularly in well-differentiated HCC. The NGR peptide selectively targets CD13, which is overexpressed in many types of tumor cells as well as neovasculature cells. In the present study, we aimed to evaluate the feasibility of utilizing 68Ga-NGR to image CD13-positive well-differentiated HCC xenografts. The in vitro cellular uptake, in vivo micro-PET/CT imaging and biodistribution studies of 68Ga-NGR and 18F-FDG were quantitatively compared in SMMC-7721-based well‑differentiated HCC xenografts. The human fibrosarcoma (HT-1080) and human colorectal adenocarcinoma (HT-29) xenografts were respectively used as positive and negative reference groups for CD13. The expression of CD13 was qualitatively verified by immunofluorescence staining and immunohistostaining studies. The expression levels of CD13 and glucose-6-phosphatase (G6Pase) were semi-quantitatively analyzed by western blotting. The in vitro SMMC-7721 cellular uptake of 68Ga‑NGR was significantly higher than that of 18F-FDG (1.23±0.11 vs. 0.515±0.14%; P<0.01). The in vivo micro-PET/CT imaging results revealed that the uptake of 68Ga-NGR in SMMC-7721-derived tumors was 2.17±0.21% ID/g (percentage of injected dose per gram of tissue), which was higher compared to that of 18F-FDG (0.73±0.26% ID/g; P<0.01); however, the tumor/liver ratio of 68Ga-NGR was 2-fold higher than that of 18F-FDG. We concluded that the uptake of 68Ga-NGR was significantly higher both in vitro and in vivo than 18F-FDG in the well‑differentiated HCC xenografts and therefore, it is promising for further clinical translation in well-differentiated HCC PET/CT diagnosis.