Development of a Novel PET Tracer [18F]AlF-NOTA-C6 Targeting MMP2 for Tumor Imaging.
The overexpression of gelatinases, that is, matrix metalloproteinase MMP2 and MMP9, has been associated with tumor progression, invasion, and metastasis. To image MMP2 in tumors, we developed a novel ligand termed [18F]AlF-NOTA-C6, with consideration that: c(KAHWGFTLD)NH2 (herein, C6) is a selective...
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| 格式: | 文件 |
| 语言: | English |
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Public Library of Science (PLoS)
2015-01-01
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| 丛编: | PLoS ONE |
| 在线阅读: | http://europepmc.org/articles/PMC4634933?pdf=render |
| _version_ | 1828879496303869952 |
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| author | Qinghua Liu Donghui Pan Chao Cheng Dazhi Zhang Anyu Zhang Lizhen Wang Hongdie Jiang Tao Wang Hongrui Liu Yuping Xu Runlin Yang Fei Chen Min Yang Changjing Zuo |
| author_facet | Qinghua Liu Donghui Pan Chao Cheng Dazhi Zhang Anyu Zhang Lizhen Wang Hongdie Jiang Tao Wang Hongrui Liu Yuping Xu Runlin Yang Fei Chen Min Yang Changjing Zuo |
| author_sort | Qinghua Liu |
| collection | DOAJ |
| description | The overexpression of gelatinases, that is, matrix metalloproteinase MMP2 and MMP9, has been associated with tumor progression, invasion, and metastasis. To image MMP2 in tumors, we developed a novel ligand termed [18F]AlF-NOTA-C6, with consideration that: c(KAHWGFTLD)NH2 (herein, C6) is a selective gelatinase inhibitor; Cy5.5-C6 has been visualized in many in vivo tumor models; positron emission tomography (PET) has a higher detection sensitivity and a wider field of view than optical imaging; fluorine-18 (18F) is the optimal PET radioisotope, and the creation of a [18F]AlF-peptide complex is a simple procedure.C6 was conjugated to the bifunctional chelator NOTA (1, 4, 7-triazacyclononanetriacetic acid) for radiolabeling [18F]AlF conjugation. The MMP2-binding characteristics and tumor-targeting efficacy of [18F]AlF-NOTA-C6 were tested in vitro and in vivo.The non-decay corrected yield of [18F]AlF-NOTA-C6 was 46.2-64.2%, and the radiochemical purity exceeded 95%. [18F]AlF-NOTA-C6 was favorably retained in SKOV3 and PC3 cells, determined by cell uptake. Using NOTA-C6 as a competitive ligand, the uptake of [18F]AlF-NOTA-C6 in SKOV3 cells decreased in a dose-dependent manner. In biodistribution and PET imaging studies, higher radioactivity concentrations were observed in tumors. Pre-injection of C6 caused a marked reduction in tumor tissue uptake. Immunohistochemistry showed MMP2 in tumor tissues.[18F]AlF-NOTA-C6 was easy to synthesize and has substantial potential as an imaging agent that targets MMP2 in tumors. |
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| id | doaj.art-92e81de8f7a847c7837b6ac0613f79be |
| institution | Directory Open Access Journal |
| issn | 1932-6203 |
| language | English |
| last_indexed | 2024-12-13T09:28:18Z |
| publishDate | 2015-01-01 |
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| spelling | doaj.art-92e81de8f7a847c7837b6ac0613f79be2022-12-21T23:52:33ZengPublic Library of Science (PLoS)PLoS ONE1932-62032015-01-011011e014166810.1371/journal.pone.0141668Development of a Novel PET Tracer [18F]AlF-NOTA-C6 Targeting MMP2 for Tumor Imaging.Qinghua LiuDonghui PanChao ChengDazhi ZhangAnyu ZhangLizhen WangHongdie JiangTao WangHongrui LiuYuping XuRunlin YangFei ChenMin YangChangjing ZuoThe overexpression of gelatinases, that is, matrix metalloproteinase MMP2 and MMP9, has been associated with tumor progression, invasion, and metastasis. To image MMP2 in tumors, we developed a novel ligand termed [18F]AlF-NOTA-C6, with consideration that: c(KAHWGFTLD)NH2 (herein, C6) is a selective gelatinase inhibitor; Cy5.5-C6 has been visualized in many in vivo tumor models; positron emission tomography (PET) has a higher detection sensitivity and a wider field of view than optical imaging; fluorine-18 (18F) is the optimal PET radioisotope, and the creation of a [18F]AlF-peptide complex is a simple procedure.C6 was conjugated to the bifunctional chelator NOTA (1, 4, 7-triazacyclononanetriacetic acid) for radiolabeling [18F]AlF conjugation. The MMP2-binding characteristics and tumor-targeting efficacy of [18F]AlF-NOTA-C6 were tested in vitro and in vivo.The non-decay corrected yield of [18F]AlF-NOTA-C6 was 46.2-64.2%, and the radiochemical purity exceeded 95%. [18F]AlF-NOTA-C6 was favorably retained in SKOV3 and PC3 cells, determined by cell uptake. Using NOTA-C6 as a competitive ligand, the uptake of [18F]AlF-NOTA-C6 in SKOV3 cells decreased in a dose-dependent manner. In biodistribution and PET imaging studies, higher radioactivity concentrations were observed in tumors. Pre-injection of C6 caused a marked reduction in tumor tissue uptake. Immunohistochemistry showed MMP2 in tumor tissues.[18F]AlF-NOTA-C6 was easy to synthesize and has substantial potential as an imaging agent that targets MMP2 in tumors.http://europepmc.org/articles/PMC4634933?pdf=render |
| spellingShingle | Qinghua Liu Donghui Pan Chao Cheng Dazhi Zhang Anyu Zhang Lizhen Wang Hongdie Jiang Tao Wang Hongrui Liu Yuping Xu Runlin Yang Fei Chen Min Yang Changjing Zuo Development of a Novel PET Tracer [18F]AlF-NOTA-C6 Targeting MMP2 for Tumor Imaging. PLoS ONE |
| title | Development of a Novel PET Tracer [18F]AlF-NOTA-C6 Targeting MMP2 for Tumor Imaging. |
| title_full | Development of a Novel PET Tracer [18F]AlF-NOTA-C6 Targeting MMP2 for Tumor Imaging. |
| title_fullStr | Development of a Novel PET Tracer [18F]AlF-NOTA-C6 Targeting MMP2 for Tumor Imaging. |
| title_full_unstemmed | Development of a Novel PET Tracer [18F]AlF-NOTA-C6 Targeting MMP2 for Tumor Imaging. |
| title_short | Development of a Novel PET Tracer [18F]AlF-NOTA-C6 Targeting MMP2 for Tumor Imaging. |
| title_sort | development of a novel pet tracer 18f alf nota c6 targeting mmp2 for tumor imaging |
| url | http://europepmc.org/articles/PMC4634933?pdf=render |
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