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Its uptake and aVb3 expression in tumors showed a linear correlation. Since aVb3 integrin is strongly expressed on activated endothelial cells during angiogenesis, we aimed to determine whether 64Cu-cyclam-\nRAFT-c(-RGDfK-)4 PET can be used to image tumor angiogenesis and monitor the antiangiogenic effect of a novel multi-targeted tyrosine kinase inhibitor, TSU-68. Athymic nude mice bearing human hepatocellular carcinoma HuH-7 xenografts, which expressed negligible aVb3 levels on the tumor cells, received intraperitoneal injections of TSU-68 or the vehicle for 14 days. Antiangiogenic effects were determined at the end of therapy in terms of 64Cu-cyclam-RAFTc(-RGDfK-)4 uptake evaluated using PET, biodistribution assay, and autoradiography, and they were compared with microvessel density (MVD) determined by CD31 immunostaining.\n64Cu-cyclam-RAFT-c(-RGDfK-)4 PET enabled clear tumor visualization by targeting the vasculature, and the biodistribution assay indicated high tumor-to-blood andtumor-to-muscle ratios of 31.6 +/- 6.3 and 6.7 +/- 1.1, respectively, 3 h after probe injection. TSU-68 significantly slowed tumor growth and reduced MVD; these findings were consistent with a significant reduction in the tumor 64Cucyclam-RAFT-c(-RGDfK-)4 uptake. Moreover, a linear correlation was observed between tumor MVD and the corresponding standardized uptake value (SUV) (r = 0.829, P = 0.011 for SUVmean; r = 0.776, P = 0.024 for SUVmax)determined by quantitative PET. Autoradiography and\nimmunostaining showed that the distribution of intratumoral radioactivity and tumor vasculature corresponded. 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Positron emission tomography imaging of tumor angiogenesis and monitoring of antiangiogenic efficacy using the novel tetrameric peptide probe 64Cu-cyclam-RAFT-c(-RGDfK-)4
https://repo.qst.go.jp/records/46527
https://repo.qst.go.jp/records/46527fb866d7e-9d5d-42f2-b47e-327c9d1f4027
Item type | 学術雑誌論文 / Journal Article(1) | |||||
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公開日 | 2013-04-15 | |||||
タイトル | ||||||
タイトル | Positron emission tomography imaging of tumor angiogenesis and monitoring of antiangiogenic efficacy using the novel tetrameric peptide probe 64Cu-cyclam-RAFT-c(-RGDfK-)4 | |||||
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 |
Jin, Zhao-Hui
× Jin, Zhao-Hui× Furukawa, Takako× Coll, Jean-Luc× Fukumura, Toshimitsu× Fujibayashi, Yasuhisa× Saga, Tsuneo× et.al× 金 朝暉× 古川 高子× 福村 利光× 藤林 康久× 佐賀 恒夫 |
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抄録 | ||||||
内容記述タイプ | Abstract | |||||
内容記述 | 64Cu-cyclam-RAFT-c(-RGDfK-)4 is a novel multimeric positron emission tomography (PET) probe foraVb3 integrin imaging. Its uptake and aVb3 expression in tumors showed a linear correlation. Since aVb3 integrin is strongly expressed on activated endothelial cells during angiogenesis, we aimed to determine whether 64Cu-cyclam- RAFT-c(-RGDfK-)4 PET can be used to image tumor angiogenesis and monitor the antiangiogenic effect of a novel multi-targeted tyrosine kinase inhibitor, TSU-68. Athymic nude mice bearing human hepatocellular carcinoma HuH-7 xenografts, which expressed negligible aVb3 levels on the tumor cells, received intraperitoneal injections of TSU-68 or the vehicle for 14 days. Antiangiogenic effects were determined at the end of therapy in terms of 64Cu-cyclam-RAFTc(-RGDfK-)4 uptake evaluated using PET, biodistribution assay, and autoradiography, and they were compared with microvessel density (MVD) determined by CD31 immunostaining. 64Cu-cyclam-RAFT-c(-RGDfK-)4 PET enabled clear tumor visualization by targeting the vasculature, and the biodistribution assay indicated high tumor-to-blood andtumor-to-muscle ratios of 31.6 +/- 6.3 and 6.7 +/- 1.1, respectively, 3 h after probe injection. TSU-68 significantly slowed tumor growth and reduced MVD; these findings were consistent with a significant reduction in the tumor 64Cucyclam-RAFT-c(-RGDfK-)4 uptake. Moreover, a linear correlation was observed between tumor MVD and the corresponding standardized uptake value (SUV) (r = 0.829, P = 0.011 for SUVmean; r = 0.776, P = 0.024 for SUVmax)determined by quantitative PET. Autoradiography and immunostaining showed that the distribution of intratumoral radioactivity and tumor vasculature corresponded. We concluded that 64Cu-cyclam-RAFT-c(-RGDfK-)4 PET can be used for in vivo angiogenesis imaging and monitoring oftumor response to antiangiogenic therapy. |
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書誌情報 |
Angiogenesis 巻 15, 号 4, p. 569-580, 発行日 2012-05 |
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ISSN | ||||||
収録物識別子タイプ | ISSN | |||||
収録物識別子 | 0969-6970 | |||||
DOI | ||||||
識別子タイプ | DOI | |||||
関連識別子 | doi 10.1007/s10456-012-9281-1 |