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Molecular imaging of tumor angiogenesis and monitoring of the antiangiogenic efficacy of a tyrosine kinase inhibitor with a novel multivalent PET probe, 64Cu-cyclam-RAFT-c(-RGDfK-)4)
https://repo.qst.go.jp/records/70780
https://repo.qst.go.jp/records/7078064587c7b-96a9-4c86-87aa-e96f5eba4eeb
| Item type | 会議発表用資料 / Presentation(1) | |||||
|---|---|---|---|---|---|---|
| 公開日 | 2012-05-29 | |||||
| タイトル | ||||||
| タイトル | Molecular imaging of tumor angiogenesis and monitoring of the antiangiogenic efficacy of a tyrosine kinase inhibitor with a novel multivalent PET 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_c94f | |||||
| 資源タイプ | conference object | |||||
| 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× 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 | aVB3 Integrin plays important roles in angiogenesis and metastasis. We have developed a novel multivalent positron emission tomography (PET) probe, 64Cu-cyclam-RAFT-c(-RGDfK-)4, for imaging aVB3 integrin, and found a strong and positive correlation between the uptake of this probe and corresponding aVB3 integrin expression levels in tumor. Since aVB3 integrin is highly expressed on activated endothelial cells during angiogenesis, the aim of present study was to determine whether 64Cu-cyclam-RAFT-c(-RGDfK-)4 PET can be used for visualization and quantification of tumor angiogenesis, and for monitoring of the effects of antiangiogenic therapy with a novel multi-targeted tyrosine kinase inhibitor TSU-68. Methods: Human hepatocellular carcinoma HuH-7 xenografts selectively expressing aVB3 integrin on tumor vessels in nude mice were used as the tumor model. PET imaging and biodistribution studies were performed at 1 and 3 h after injection of 64Cu-cyclam-RAFT-c(-RGDfK-)4 for tumor angiogenesis imaging. Tumor-bearing mice were treated with daily i.p. injection of TSU-68 for 14 consecutive days or vehicle alone. Body weight and tumor volume were measured throughout the study, and on subsequent day after the final drug administration, therapeutic efficiency was evaluated in terms of (1) tumor tracer uptake measured by biodistribution assay, PET scan, and autoradiography, and (2) tumor microvessel density (MVD) determined by CD31 immunostaining. Autoradiography and immunostaining were performed on same tumor sections to align the intratumoral tracer distribution with the tumor vasculature. Results: 64Cu-cyclam-RAFT-c(-RGDfK-)4 PET allowed clear tumor visualization via targeting the tumor vasculature, and biodistribution study indicated high tumor-to-blood and tumor-to-muscle ratios. TSU-68 administration significantly slowed the tumor growth and resulted in significant reduction in MVD, which was consistent with a significant reduction in tumor 64Cu-cyclam-RAFT-c(-RGDfK-)4 uptake. Moreover, significant correlation was obtained between tumor MVD and corresponding standardized uptake value determined by quantitative PET. Autoradiography and immunostaining showed the intratumoral 64Cu-cyclam-RAFT-c(-RGDfK-)4 radioactivity distribution matched to the tumor vasculature. Conclusion: 64Cu-cyclam-RAFT-c(-RGDfK-)4 PET could be used for in vivo angiogenesis imaging and monitoring of tumor response to antiangiogenic therapy. | |||||
| 会議概要（会議名, 開催地, 会期, 主催者等） | ||||||
| 内容記述タイプ | Other | |||||
| 内容記述 | 日本分子イメージング学会第７回学術集会 | |||||
| 発表年月日 | ||||||
| 日付 | 2012-05-25 | |||||
| 日付タイプ | Issued | |||||
