論文 - 詳細
| RRC ID | 18217 |
|---|---|
| 著者 | Wang F, Fang W, Zhang MR, Zhao M, Liu B, Wang Z, Hua Z, Yang M, Kumata K, Hatori A, Yamasaki T, Yanamoto K, Suzuki K. |
| タイトル | Evaluation of chemotherapy response in VX2 rabbit lung cancer with 18F-labeled C2A domain of synaptotagmin I. |
| ジャーナル | J Nucl Med |
| Abstract |
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. |
| 巻・号 | 52(4) |
| ページ | 592-9 |
| 公開日 | 2011-4-1 |
| DOI | 10.2967/jnumed.110.081588 |
| PII | jnumed.110.081588 |
| PMID | 21421722 |
| PMC | PMC3866918 |
| MeSH | Animals Antineoplastic Agents, Phytogenic / therapeutic use Apoptosis / drug effects Caspase 3 / metabolism Chromatography, High Pressure Liquid Electrophoresis, Polyacrylamide Gel Feasibility Studies Fluorine Radioisotopes Humans Image Processing, Computer-Assisted Indicators and Reagents Isotope Labeling / methods Jurkat Cells Lung Neoplasms / diagnostic imaging* Lung Neoplasms / drug therapy* Male Mice Molecular Imaging Paclitaxel / therapeutic use Positron-Emission Tomography Rabbits Radiopharmaceuticals* / chemistry Radiopharmaceuticals* / pharmacokinetics Synaptotagmin I* / chemistry Synaptotagmin I* / pharmacokinetics Tissue Distribution |
| IF | 7.887 |
| 引用数 | 23 |
| WOS 分野 | RADIOLOGY, NUCLEAR MEDICINE & MEDICAL IMAGING |
| リソース情報 | |
| ヒト・動物細胞 | Jurkat(RCB0806) |