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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 micro-PET/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 68 Ga-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.
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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.
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Objective To explore the optimal conditions of preparing 68Ga-DOTA-iNGR (NGR peptide containing CendR motif),to evaluate its biodistribution in normal mice and to perform microPET imaging in tumor-bearing nude mice.Methods 68Ga fresh eluent (200 μl,92.5-129.5 MBq) obtaining with 68Ge-68Ga radionuclide generator was used to label DOTA-iNGR.The optimal conditions of labeling including pH,temperature,reacting time and concentration of DOTA-iNGR were determined.Then,the in vitro and in vivo stability and octanol/water partition coefficient of 68Ga-DOTA-iNGR were further analyzed.The biodistribution in normal Kunming mice was examined at 10,20,40,60 and 120 min after injection of 68Ga-DOTA-iNGR.Nude mice bearing HT-1080 (CDl3-positive) and HT-29 (CDl3-negative) tumors were established and underwent microPET imaging at 1 h after the intravenous injection of 68Ga-DOTA-iNGR.Data were analyzed using independent-sample t test.Results The optimal conditions of labeling was mixing 2 μg DOTA-iNGR peptide with 200 μl 68Ga (92.5-129.5 MBq) at pH 4.0,temperature 90-100 ℃ for 5-10 min.Under this condition,labeling rate reached (97.5± 1.3)％.The radiochemical purity of 68Ga-DOTA-iNGR in both saline (room temperature) and mouse serum (37 C) were both above 95％ after 4 h incubation,and the radiochemical purity in urine was greater than 85％ after 1 h metabolism in vivo.The partition coefficient was-2.71±0.18.In normal mice,majority of 68Ga-DOTA-iNGR was excreted from kidneys with a rapid clearance from blood.The in vivo microPET imaging showed that 68Ga-DOTA-iNGR was remarkably accumulated in the CD13-positive HT-1080 tumor.Conclusions Labeling DOTA-iNGR with 68Ga under our condition is a simple and efficient procedure with high labeling rate and high specificity.The product 68Ga-DOTA-iNGR has high stability,ideal biodistribution,and specific binding to CD13-positive tumor,which means that it's a very promising molecular probe for noninvasively detecting CD13-positive tumor.
