目的定量对比18F-FDG及新生血管靶向探针68Ga-NGR对高分化肝癌裸鼠模型的micro.PET/CT显像效果。方法以CDl3+的SMMC-7721肝癌细胞及裸鼠模型作为实验组,CDl3+的HT-1080纤维肉瘤细胞及裸鼠作为阳性对照,以及CDl3-的HT.29直肠癌细胞及裸鼠模型作为阴性对照。用Westernblot检测CD13及葡萄糖-6-磷酸酯酶(G6Pase)在3种肿瘤细胞中的表达情况。通过体外细胞摄取实验以及microPET/CT显像分别对18F.FDG及68Ga-NGR在3种肿瘤中的摄取进行评估。最后对肿瘤组织行CDl3受体免疫组织化学染色。采用两样本t检验进行数据比较。结果细胞摄取实验示。Ga—NGR在SMMC.7721及HT.1080细胞中的摄取较HT-29细胞高,SMMC-7721细胞中68Ga—NGR摄取较18F-FDG摄取高。体内microPET/CT也显示SMMC-7721肝癌的68Ga-NGR摄取明显高于18F.FDG摄取,分别为(2.17±0.21)%ID/g和(O.73±0.26)%ID/g(t=8.826,P〈0.01);在68Ga-1080肿瘤中,68Ga-NGR及18F.FDG均有较高的摄取[(2.46±0.23)%ID/g、(3.47±0.31)%ID/g];HT-29肿瘤的68Ga—NGR摄取明显低于18F.FDG摄取:(0.67±0.20)%ID/g与(3.17±0.29)%ID/g;t=4.221,P〈0.01。68Ga-NGR在SMMC.7721肝癌中的肿瘤/肝脏摄取比值为2.05±0.16,是18F.FDG的2.03倍。Westernblot及免疫组织化学结果验证了3种肿瘤的表达特性:HT.1080(CDl3’,G6Pase-),SMMC.7721(CDl3’,G6Pase’),HT-29(CDl3-,G6Pase-)。结论高分化肝癌模型鼠的68Ga-NGR摄取高于“F—FDG摄取,提示该探针有用于肝癌的临床转化潜力。CDl3及G6Pase分子分型不同的3种肿瘤对胡Ga—NGR及“F.FDG摄取的区别,预示着分子影像技术具有评估相关分子分型的潜力。
Objective -To quantitatively compare the diagnostic capability of 6SGa-NGR and 18F- FDG in well-differentiated hepatocellular carcinoma (HCC) bearing mice by microPET/CT imaging. Methods The in vitro cellular uptake, in vivo microPET/CT imaging and biodistribution studies of 6SGa-NGR and 18F- FDG were quantitatively compared in SMMC-7721-based well-differentiated HCC. The human fibrosarcoma (HT-1080) and human colorectal adenocarcinoma (HT-29) cells/xenografts were respectively used as posi- tive and negative reference groups for CD13. The expression of CD13 was qualitatively verified by iinmunohis- tostaining. The levels of CD13 and glucose-6-phosphatase (G6Pase) were semi-quantitatively analyzed by Western blot test for all 3 types of tumors. Two-sample t test was used for data analysis. Results The in vitro cellular uptake showed that the 6SGa-NGR uptake in SMMC-7721 and HT-1080 cells was higher than that in HT-29 cells, and the 6SGa-NGR uptake was higher than laF-FDG uptake in SMMC-7721 cells. The in vivo micro-PET/CT imaging results revealed that the uptake of 6SGa-NGR in SMMC-7721 tumor was (2.17±0.21) %ID/g, remarkably higher compared to (0.73±0.26) %ID/g of lS F-FDG uptake (t = 8.826, P〈0.01). The tumor/ liver ratio of 6SGa-NGR was 2.05±0.16, which was 2.03-fold higher than that of 18SF-FDG. In the HT-1080 tumors, the uptakes of 6SGa-NGR and ISF-FDG were both high, and the values were (2.46±0. 23) %ID/g, (3.47±0.31) %ID/g. The uptake of 6SGa-NGR was significantly lower than that of lSF-FDG in HT-29 tumors: (0.67±0.20) %ID/g vs (3.17-+0.29) %ID/g; t=4.221, P〈O.O1. Western blot and immunohis- tostaining results were as follows : HT-1080( CDI3+, G6Pase-) , SMMC-7721 ( CD13+, G6Pase+ ) , HT-29 (CD13-, G6Pase-). Conclusions The uptake of 6SGa-NGR is higher than laF-FDG uptake in SMMC- 7721 tumor beating mice, therefore it is worthwhile to consider the feasibility of clinical translation for PET/ CT in diagnosis of HCC. Furthermore, b