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Objective: The C2A domain of synaptotagmin I can target apoptotic cell by binding to exposed anionic phospholipids.The goal of this study is to synthesize and develop 18F-labeled C2A-GST as a molecular probe for the detection of apoptosis and to assess response of paclitaxel chemotherapy in VX2 rabbit lung cancer.Methods: 18F-C2A-GST was prepared by labeling C2A-GST with N-succinimidyl 4-18F-fluorobenzoate (18F-SFB).18F-C2A-GST was confirmed by SDS-PAGE and high performance liquid chromatography, respectively.The binding of 18F-C2A-GST toward apoptosis was validated in vitro using camptothecin-induced Jurkat cells.Biodistribution of 18F-C2A-GST was determined in mice by dissection method and small-animal PET.Single dose paclitaxel was used to induce apoptosis in rabbits bearing VX2 tumor (n =6), while 2 VX2 rabbits without treatment served as control.18F-C2A-GST PET was performed before and 72 h after therapy,18F-FDG PET/CT was also performed before treatment.To confirm the presence of apoptosis,tumor tissue analysis was performed and activated Caspase3 was measured.Results: 18F-C2A-GST was obtained with radiochemical purity > 95% and stable 4 h after formulation.18F-C2A-GST bound apoptotic cells specifically.Biodistribution in mice showed that 18F-C2A-GST mainly excreted from kidney, and rapidly cleared from blood and nonspecific organs.High focal uptake of 18F-C2A-GST in the tumor area was visualized after therapy, whereas no significant uptake before therapy was found in the tumor which is 18F-FDG avid foci.SUVmax of posttherapy was 0.47 ± 0.28, significantly higher than that of untreated group (0.009 ± 0.001; P < 0.001).The apoptotic index was 79.81 ± 8.73% in treated group, significantly higher than that in control (5.03 ± 0.81%; P < 0.001).Activated Caspase-3 after paclitaxel treatment increased to 69.55 ± 16.27% and was significantly higher than that in control (12.26 ± 5.39%; P < 0.001).Conclusion: 18F-C2A-GST was easily synthesized by conjugation with 18F-SFB and manifested a favorable biodistribution.Our results demonstrate the feasibility of 18F-C2A-GST for the early detection of apoptosis after chemotherapy in VX2 lung cancer model which could imitate the human lung cancer initiation, development and progress.