| Copper-64-diacetyl-bis (N4-methylthiosemicarbazone) accumulates in rich regions of CD133+ highly tumorigenic cells in mouse colon carcinoma. | |
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MedLine Citation:
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PMID: 20447549 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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INTRODUCTION: (64)Cu-diacetyl-bis (N(4)-methylthiosemicarbazone) ((64)Cu-ATSM) is a potential imaging agent of hypoxic tumor for use with PET. Recent literature demonstrated that cancer cells expressing CD133, which is a frequently used marker for so-called cancer stem cells or cancer stem cell-like cells (collectively referred to here as CSCs), contribute to tumor's therapeutic resistance and metastasis ability. Culturing under hypoxia is also reported to enlarge the proportion of CD133(+) cells, which would indicate survival advantage of CD133(+) cells under hypoxia. Here, we investigated the relationships between (64)Cu-ATSM accumulation and existence of CD133(+) cells using mouse colon carcinoma (colon-26) tumor. METHODS: Intratumor distribution of (64)Cu-ATSM and (18)F-fluorodeoxyglucose ((18)FDG) was compared with immunohistochemical staining for CD133 with a colon-26 model. In vitro characterization of CD133(+) colon-26 cells was also performed. RESULTS: In colon-26 tumors, (64)Cu-ATSM localized preferentially in regions with a high density of CD133(+) cells. The percentage of CD133(+) cells was 11-fold higher in (64)Cu-ATSM high-uptake regions compared with (18)FDG high- (but (64)Cu-ATSM low-) uptake regions. CD133(+) colon-26 cells showed characteristics previously linked with CSCs in other cancer cell lines, such as high colony-forming ability, high tumor-initiating ability and enrichment under hypoxic cultivation. The proportion of CD133(+) cells was enlarged by culturing under glucose starvation as well as hypoxia, and (64)Cu-ATSM uptake was increased under such conditions. CONCLUSIONS: Our findings showed that, in colon-26 tumors, (64)Cu-ATSM accumulates in rich regions of CD133(+) cells with characteristics of CSCs. Therefore (64)Cu-ATSM could be a potential imaging agent for rich regions of CD133(+) cells, associated with CSCs, within tumors. |
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Authors:
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Yukie Yoshii; Takako Furukawa; Yasushi Kiyono; Ryo Watanabe; Atsuo Waki; Tetsuya Mori; Hiroshi Yoshii; Myungmi Oh; Tatsuya Asai; Hidehiko Okazawa; Michael J Welch; Yasuhisa Fujibayashi |
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Publication Detail:
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Type: Journal Article; Research Support, Non-U.S. Gov't Date: 2010-02-10 |
Journal Detail:
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Title: Nuclear medicine and biology Volume: 37 ISSN: 1872-9614 ISO Abbreviation: Nucl. Med. Biol. Publication Date: 2010 May |
Date Detail:
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Created Date: 2010-05-07 Completed Date: 2010-08-17 Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 9304420 Medline TA: Nucl Med Biol Country: England |
Other Details:
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Languages: eng Pagination: 395-404 Citation Subset: IM |
Copyright Information:
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(c) 2010 Elsevier Inc. All rights reserved. |
Affiliation:
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Biomedical Imaging Research Center, University of Fukui, Eiheiji, Fukui 910-1193, Japan. |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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Animals Antigens, CD / metabolism* Biological Transport Cell Hypoxia Cell Line, Tumor Colonic Neoplasms / genetics, metabolism*, pathology* Copper Radioisotopes* Fluorodeoxyglucose F18 / metabolism Gene Expression Regulation, Neoplastic Glucose / metabolism Glycoproteins / metabolism* Male Mice Neoplastic Stem Cells / metabolism, pathology Organometallic Compounds / metabolism* Peptides / metabolism* Radioactive Tracers Thiosemicarbazones / metabolism* |
| Chemical | |
Reg. No./Substance:
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0/AC133 antigen; 0/Antigens, CD; 0/Copper Radioisotopes; 0/Glycoproteins; 0/Organometallic Compounds; 0/Peptides; 0/Radioactive Tracers; 0/Thiosemicarbazones; 0/copper (II) diacetyl-di(N(4)-methylthiosemicarbazone); 50-99-7/Glucose; 63503-12-8/Fluorodeoxyglucose F18 |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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