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

Feng Wang, Wei Fang, Ming Rong Zhang*, Ming Zhao, Biao Liu, Zizheng Wang, Zichun Hua, Min Yang, Katsushi Kumata, Akiko Hatori, Tomoteru Yamasaki, Kazuhiko Yanamoto, Kazutoshi Suzuki

*Corresponding author for this work

Research output: Contribution to journalArticle

24 Scopus citations

Abstract

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 18F-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: 18F-C2A-GST was prepared by labeling C2A-GST with N-succinimidyl 4-18F-fluorobenzoate (18F-SFB). 18F-C2A-GST was confirmed by high-performance liquid chromatography and sodium dodecyl sulfate polyacrylamide gel electrophoresis. 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 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. 18FC2A- GST PET was performed before and at 72 h after therapy, and 18F-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: 18FC2A- GST was obtained with more than 95% radiochemical purity and was stable for 4 h after formulation. 18F-C2A-GST bound apoptotic cells specifically. Biodistribution in mice showed that 18F-C2A-GST mainly excreted from the kidneys and rapidly cleared from blood and nonspecific organs. High focal uptake of 18F-C2A-GST in the tumor area was determined after therapy, whereas no significant uptake before therapy was found in the tumor with 18F-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: 18F-C2A-GST was easily synthesized by conjugation with 18F-SFB and manifested a favorable biodistribution. Our results demonstrated the feasibility of 18FC2A- GST for the early detection of apoptosis after chemotherapy in a VX2 lung cancer model that could imitate.

Original languageEnglish (US)
Pages (from-to)592-599
Number of pages8
JournalJournal of Nuclear Medicine
Volume52
Issue number4
DOIs
StatePublished - Apr 1 2011

Keywords

  • Apoptosis
  • C2A domain
  • F-labeled C2A-GS.T.
  • PE.T.
  • Synaptotagmin I

ASJC Scopus subject areas

  • Radiology Nuclear Medicine and imaging

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    Wang, F., Fang, W., Zhang, M. R., Zhao, M., Liu, B., Wang, Z., Hua, Z., Yang, M., Kumata, K., Hatori, A., Yamasaki, T., Yanamoto, K., & Suzuki, K. (2011). Evaluation of chemotherapy response in VX2 rabbit lung cancer with 18F-Labeled C2A domain of synaptotagmin I. Journal of Nuclear Medicine, 52(4), 592-599. https://doi.org/10.2967/jnumed.110.081588