Abstract
MG7-Ag, a specific gastric cancer-associated antigen, can be used to non-invasively monitor gastric cancer by molecular imaging with positron emission tomography/computed tomography (PET/CT). In this study, we prepared and evaluated a 68Ga-labeled MG7 antibody as a molecular probe for nanoPET/CT imaging of gastric cancer in a BGC-823 tumor xenografted mouse model. Macrocyclic chelator 1,4,7-triazacyclononane-N,N0,N00-triacetic acid (NOTA)-conjugated MG7 antibody was synthesized and radiolabeled with 68Ga (t1/2 = 67.71 min). Then, 68Ga-NOTA-MG7 was tested using in vitro cytological studies, in vivo nanoPET/CT and Cerenkov imaging studies as well as ex vivo biodistribution and histology studies. The in vitro experiments demonstrated that 68Ga-NOTA-MG7 has an excellent radiolabeling efficiency of approximately 99% without purification, and it is stable in serum after 120 min of incubation. Cell uptake and retention studies confirmed that 68Ga-NOTA-MG7 has good binding affinity and tumor cell retention. For the nanoPET imaging study, the predominant uptake of 68Ga-NOTA-MG7 was visualized in tumor, liver and kidneys. The tumor uptake reached at its peak (2.53 ± 0.28%ID/g) at 60 min pi. Cherenkov imaging also confirmed the specificity of tumor uptake. Moreover, the biodistribution results were consistent with the quantification data of nanoPET/CT imaging. Histologic analysis also demonstrated specific staining of BGC-823 tumor cell lines.
Highlights
The radiolabeling efficiency of 68Ga-NOTA-MG7 was evaluated using a radio-thin-layer chromatography (TLC) method and the radiolabeling efficiency was approximately 99% without purification, while the free 68Ga31 remained at the origin of the TLC plate
In this study, we have successfully developed a targeted probe for positron emission tomography/computed tomography (PET/CT) imaging of gastric cancer
With the combination of 68Galabeled MG7 antibody probe and positron emission tomography (PET)/CT, we confirmed that molecular imaging of gastric cancer can be achieved with PET/CT imaging
Summary
Radiochemistry, log P value and in vitro stability. The radiolabeling efficiency of 68Ga-NOTA-MG7 was evaluated using a radio-thin-layer chromatography (TLC) method and the radiolabeling efficiency was approximately 99% without purification, while the free 68Ga31 remained at the origin of the TLC plate. After 30 min of incubation, approximately 2.64% of 68Ga-NOTA-MG7 uptake in BGC-823 cells was detected. The cell efflux study showed that 68Ga-NOTA-MG7 had relatively good cell retention in BGC-823 cells during the 60 min of cell efflux study, and approximately 2.15% (from 8.57% to Figure 2 | Laser scanning confocal microscopy imaging of different cell lines (MKN-28, SGC-7901, BGC-823, MKN-45, and GES, HT-29) after incubation with MG7 antibody showed that the expression of MG7-Ag was in the cell membrane and cytoplasm in each of gastric cell line, and there was little MG7-Ag expression in the normal gastric epithelial cell lines (GES) and colon cancer cell lines (HT-29). The tumor-targeting efficacy and pharmacokinetic pattern of 68Ga-NOTA-MG7 were evaluated in nude mice bearing BGC-823 gastric cancer xenograft tumors (n 5 3) at multiple time points (30, 60 and 90 min) with static scans (Fig. 4a). Cerenkov imaging was used to evaluate the tumor-targeting efficacy of 68Ga-NOTA-MG7 at different time points (30, 60 and 90 min). Uptake of 68Ga-NOTA-MG7 in the liver and kidney was largely unrelated to MG7 binding and more likely attributed to clearance of the tracer (Fig. 7)
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