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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.

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.