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Evaluation of Chemotherapy Response in VX2 Rabbit Lung Cancer with 18F-Labeled C2A Domain of Synaptotagmin I
https://repo.qst.go.jp/records/46040
https://repo.qst.go.jp/records/4604078b87851-6ed2-4fbb-ac80-e84af73dd159
| Item type | 学術雑誌論文 / Journal Article(1) | |||||
|---|---|---|---|---|---|---|
| 公開日 | 2011-05-20 | |||||
| タイトル | ||||||
| タイトル | Evaluation of Chemotherapy Response in VX2 Rabbit Lung Cancer with 18F-Labeled C2A Domain of Synaptotagmin I | |||||
| 言語 | ||||||
| 言語 | eng | |||||
| 資源タイプ | ||||||
| 資源タイプ識別子 | http://purl.org/coar/resource_type/c_6501 | |||||
| 資源タイプ | journal article | |||||
| アクセス権 | ||||||
| アクセス権 | metadata only access | |||||
| アクセス権URI | http://purl.org/coar/access_right/c_14cb | |||||
| 著者 |
WANG, Feng
× WANG, Feng× Fang, Wei× Zhang, Ming-Rong× Kumata, Katsushi× Hatori, Akiko× Yamasaki, Tomoteru× Yanamoto, Kazuhiko× Suzuki, Kazutoshi× 王 峰× Ｆａｎｇ Ｗｅｉ× 張 明栄× 熊田 勝志× 羽鳥 晶子× 山崎 友照× 柳本 和彦× 鈴木 和年 |
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| 抄録 | ||||||
| 内容記述タイプ | Abstract | |||||
| 内容記述 | 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. 18F-C2A-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: 18F-C2A-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 18F-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. | |||||
| 書誌情報 |
Journal of Nuclear Medicine 巻 52, 号 4, p. 592-599, 発行日 2011-04 |
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| ISSN | ||||||
| 収録物識別子タイプ | ISSN | |||||
| 収録物識別子 | 0161-5505 | |||||
