18F—FDG和68Ga—NGR探针在高分化肝癌裸鼠肿瘤中的microPET／CT定量比较

Quantitative comparison of 68Ga-NGR and 18SF-FDG uptake in well-differentiated hepatocellular carci- noma bearing mice

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, because of the difference in 6SGa-NGR and 1SF-FDG avidities in tumors with different molecular phenotypes of CD13 and G6Pase, there is an underlying potential for molec- ular imaging in the determination of molecular phenotypes.