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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/70539
https://repo.qst.go.jp/records/70539570843c0-acdd-4f5f-a1df-53dd86d550ac
| Item type | 会議発表用資料 / Presentation(1) | |||||
|---|---|---|---|---|---|---|
| 公開日 | 2011-09-20 | |||||
| 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× Galibert, Mathieu× 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 | Angiogenesis plays important roles in tumor growth and metastasis, and has been increasingly recognized as an essential target for tumor imaging and therapy. Positron emission tomography (PET) is one of the most promising tools for noninvasive detection and quantification of molecular activities. The cell adhesion protein, alfaVbeta-3-integrin, is highly expressed on the activated vascular endothelial cells during angiogenesis. We have developed a novel multivalent PET probe, 64Cu-cyclam-RAFT-c(-RGDfK-)4, for alfaVbeta3-targeted imaging, and found a strong and positive correlation between the tumor uptake of this probe and the corresponding tumor alfaVbeta 3 expression levels. Our present study is to subsequently investigate the potential of this PET probe for visualization and quantification of tumor angiogenesis and furthermore for monitoring of the therapeutic efficacy of a tyrosine kinase inhibitor (TKI) as an antiangiogenic drug. Methods: A hypervascular subcutaneous xenograft of a alfaVbeta3-negative human hepatocellular carcinoma cell line (HCC) in athymic nude mice was used as a tumor angiogenesis model for the present study. PET imaging and biodistribution studies were performed at 1 or 3 h after probe administration, and autoradiography and immunostaining of serial frozen tumor sections were carried out to compare the intratumoral distribution of the probe and that of microvasculature. Another cohort of HCC tumor-bearing mice were divided into 2 groups: vehicle-treated control group and TKI-treated antiangiogenic therapy group. Mouse body weight and tumor size were measured throughout the study. After 2 weeks of treatment, tumor microvessel density (MVD), tumor uptake of the probe measured by biodistribution study and PET imaging were compared between the control and treatment group. Results: Biodistribution and PET studies revealed the favorable tumor uptake of 64Cu-cyclam-RAFT-c(-RGDfK-)4 with high tumor-to-background contrast, and autoradiography and immunostaining demonstrated the approximate colocalization of the probe and microvasculature. Antiangiogenic therapy did not show obvious side effects, and could delay the tumor growth although the significant difference in tumor volumes was not obtained between the treatment and control groups. Antiangiogenic therapy resulted in obvious reduction of tumor MVD. The corresponding decrease in tumor uptake of 64Cu-cyclam-RAFT-c(-RGDfK-)4 was expected from biodistribution and PET studies. Conclusion: 64Cu-cyclam-RAFT-c(-RGDfK-)4-based PET is able to visualize tumor angiogenesis by targeting the alfaVbeta3-integrin, and would be useful for monitoring the relatively early 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 | 2011 World Molecular Imaging Congress (WMIC) | |||||
| 発表年月日 | ||||||
| 日付 | 2011-09-10 | |||||
| 日付タイプ | Issued | |||||
