Evaluation of chemotherapy response in VX2 rabbit lung cancer with 18F-labeled C2A domain of synaptotagmin I.

Autor:	Wang F; Nanjing First Hospital, Nanjing Medical University, Nanjing, China., Fang W, Zhang MR, Zhao M, Liu B, Wang Z, Hua Z, Yang M, Kumata K, Hatori A, Yamasaki T, Yanamoto K, Suzuki K
Jazyk:	angličtina
Zdroj:	Journal of nuclear medicine : official publication, Society of Nuclear Medicine [J Nucl Med] 2011 Apr; Vol. 52 (4), pp. 592-9. Date of Electronic Publication: 2011 Mar 18.
DOI:	10.2967/jnumed.110.081588
Abstrakt:	Unlabelled: The C2A domain of synaptotagmin I can target apoptotic cells by binding to exposed anionic phospholipids. The goal of this study was to synthesize and develop (18)F-labeled C2A-glutathione-S-transferase (GST) as a molecular imaging probe for the detection of apoptosis and to assess the response of paclitaxel chemotherapy in VX2 rabbit lung cancer. Methods: (18)F-C2A-GST was prepared by labeling C2A-GST with N-succinimidyl 4-(18)F-fluorobenzoate ((18)F-SFB). (18)F-C2A-GST was confirmed by high-performance liquid chromatography and sodium dodecyl sulfate polyacrylamide gel electrophoresis. The binding of (18)F-C2A-GST toward apoptosis was validated in vitro using camptothecin-induced Jurkat cells. Biodistribution of (18)F-C2A-GST was determined in mice by a dissection method and small-animal PET. Single-dose paclitaxel was used to induce apoptosis in rabbits bearing VX2 tumors (n = 6), and 2 VX2 rabbits without treatment served as control. (18)F-C2A-GST PET was performed before and at 72 h after therapy, and (18)F-FDG PET/CT was also performed before treatment. To confirm the presence of apoptosis, tumor tissue was analyzed and activated caspase-3 was measured. Results: (18)F-C2A-GST was obtained with more than 95% radiochemical purity and was stable for 4 h after formulation. (18)F-C2A-GST bound apoptotic cells specifically. Biodistribution in mice showed that (18)F-C2A-GST mainly excreted from the kidneys and rapidly cleared from blood and nonspecific organs. High focal uptake of (18)F-C2A-GST in the tumor area was determined after therapy, whereas no significant uptake before therapy was found in the tumor with (18)F-FDG-avid foci. The maximum standardized uptake value after therapy was 0.47 ± 0.28, significantly higher than that in the control (0.009 ± 0.001; P < 0.001). The apoptotic index was 79.81% ± 8.73% in the therapy group, significantly higher than that in the 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 the control (12.26% ± 5.39%; P < 0.001). Conclusion: (18)F-C2A-GST was easily synthesized by conjugation with (18)F-SFB and manifested a favorable biodistribution. Our results demonstrated the feasibility of (18)F-C2A-GST for the early detection of apoptosis after chemotherapy in a VX2 lung cancer model that could imitate the human lung cancer initiation, development, and progress.
Databáze:	MEDLINE
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