Quantitative comparison of 68Ga-NGR and 18F-FDG uptake in well-differentiated hepatocellular carcinoma bearing mice

Abstract

Objective To quantitatively compare the diagnostic capability of 68Ga-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 68Ga-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 positive and negative reference groups for CD13. The expression of CD13 was qualitatively verified by immunohistostaining. 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 68Ga-NGR uptake in SMMC-7721 and HT-1080 cells was higher than that in HT-29 cells, and the 68Ga-NGR uptake was higher than 18F-FDG uptake in SMMC-7721 cells. The in vivo microPET/CT imaging results revealed that the uptake of 68Ga-NGR in SMMC-7721 tumor was (2.17±0.21) %ID/g, remarkably higher compared to (0.73±0.26) %ID/g of 18F-FDG uptake (t=8.826, P<0.01). The tumor/liver ratio of 68Ga-NGR was 2.05±0.16, which was 2.03-fold higher than that of 18F-FDG. In the HT-1080 tumors, the uptakes of 68Ga-NGR and 18F-FDG were both high, and the values were (2.46±0.23) %ID/g, (3.47±0.31) %ID/g. The uptake of 68Ga-NGR was significantly lower than that of 18F-FDG in HT-29 tumors: (0.67±0.20) %ID/g vs (3.17±0.29) %ID/g; t=4.221, P<0.01. Western blot and immunohistostaining results were as follows: HT-1080(CD13+ , G6Pase-), SMMC-7721(CD13+ , G6Pase+ ), HT-29(CD13-, G6Pase-). Conclusions The uptake of 68Ga-NGR is higher than 18F-FDG uptake in SMMC-7721 tumor bearing 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 68Ga-NGR and 18F-FDG avidities in tumors with different molecular phenotypes of CD13 and G6Pase, there is an underlying potential for molecular imaging in the determination of molecular phenotypes. Key words: Liver neoplasms; Positron-emission tomography; Tomography, X-ray computed; Gallium radioisotopes; Asparagine-glycine-arginine; Deoxyglucose; Mice, nude