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Noninvasive visualization and quantification of tumor a(V)B(3) integrin expression using a novel positron emission tomography probe, (64)Cu-cyclam-RAFT-c(-RGDfK-)4.
https://repo.qst.go.jp/records/46345
https://repo.qst.go.jp/records/463459c6b7690-6e22-4094-8514-f47c8aa74ad7
| Item type | 学術雑誌論文 / Journal Article(1) | |||||
|---|---|---|---|---|---|---|
| 公開日 | 2012-06-08 | |||||
| タイトル | ||||||
| タイトル | Noninvasive visualization and quantification of tumor a(V)B(3) integrin expression using a novel positron emission tomography probe, (64)Cu-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× Galibert, Mathieu× Coll, Jean-Luc× Fukumura, Toshimitsu× Saga, Tsuneo× Fujibayashi, Yasuhisa× et.al× 金 朝暉× 古川 高子× 福村 利光× 佐賀 恒夫× 藤林 康久 |
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| 抄録 | ||||||
| 内容記述タイプ | Abstract | |||||
| 内容記述 | INTRODUCTION: \nThe a(V)B(3) integrin is a well-known transmembrane receptor involved in tumor invasion, angiogenesis and metastasis. Our aim was to evaluate a novel positron emission tomography (PET) probe, (64)Cu-cyclam-RAFT-c(-RGDfK-)(4), for noninvasive visualization and quantification of a(V)B(3) integrin expression. \nMETHODS: \nRAFT-c(-RGDfK-)(4), a tetrameric cyclic Arg-Gly-Asp (RGD)-based peptide, was conjugated with a bifunctional chelator, 1,4,8,11-tetraazacyclotetradecane (cyclam), radiolabeled with the positron emitter (64)Cu and evaluated in vitro by cell binding and competitive inhibition assays and in vivo by biodistribution and receptor blocking studies, and PET imaging. The following cell lines, human embryonic kidney HEK293(B(1)) [a(V)B(3)-negative] and HEK293(B(3)) [a(V)B(3)-overexpressing] and human glioblastoma U87MG [naturally expressing a(V)B(3)], together with their subcutaneous xenografts in athymic nude mice, were used for the present study. The expression levels of a(V)B(3) on these cell lines and tumor xenografts were analyzed by flow cytometry and sodium dodecyl sulfate-polyacrylamide gel electrophoresis/autoradiography, respectively. \nRESULTS: \n(64)Cu-cyclam-RAFT-c(-RGDfK-)(4) demonstrated the in vitro and in vivo specificity for the a(V)B(3) integrin and displayed rapid blood clearance, predominantly renal excretion and low uptake in nontumor tissues. Tumor uptake of (64)Cu-cyclam-RAFT-c(-RGDfK-)(4) (3 h postinjection) in HEK293(B(3)) (high levels of a(V)B(3)), U87MG (moderate levels of a(V)B(3)) and HEK293(B(1)) (undetectable levels of a(V)B(3)) tumors was 9.35%+-1.19%, 3.46%+-0.45% and 1.18%+-0.30% injected dose per gram, respectively, with a strong and positive correlation with the tumor a(V)B(3)expression levels (correlation coefficient=0.967; P<.0001). Positron emission tomographic images showed that a(V)B(3)-positive tumors were clearly visualized with high tumor-to-background contrast, and agreed well with the biodistribution results. \nCONCLUSION: \n(64)Cu-cyclam-RAFT-c(-RGDfK-)(4) exhibits potential for noninvasively quantifying a(V)B(3) expression. |
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| 書誌情報 |
Nuclear Medicine and Biology 巻 38, 号 4, p. 529-540, 発行日 2011-02 |
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| ISSN | ||||||
| 収録物識別子タイプ | ISSN | |||||
| 収録物識別子 | 0969-8051 | |||||
| DOI | ||||||
| 識別子タイプ | DOI | |||||
| 関連識別子 | 10.1016/j.nucmedbio.2010.11.008 | |||||
