| Cell line-dependent differences in uptake and retention of the hypoxia-selective nuclear imaging agent Cu-ATSM. | |
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MedLine Citation:
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PMID: 16026709 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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BACKGROUND: Cu-diacetyl-bis(N(4)-methylthiosemicarbazone) [Cu-ATSM] is a potential marker for tumor hypoxia that has been under evaluation for clinical use. In this study, we examined the mechanisms underlying the uptake of (64)Cu in cells incubated with (64)Cu-ATSM. METHODS: The in vitro uptake of (64)Cu was determined as a function of oxygenation conditions and incubation time with (64)Cu-ATSM using four and two tumor cell lines of human origin and rodent origin, respectively. Additionally, the rate of (64)Cu efflux and Cu-ATSM metabolism was determined. RESULTS: (64)Cu accumulation is rapid during the first 0.5-1 h of incubation. It is highest in anoxic cells but is also significant in normoxic cells. After this initial period, the level of intracellular (64)Cu varies depending on the cell line and the oxygenation conditions and, in some circumstances, may decrease. During the first 0.5-1 h, the ratio of (64)Cu levels between anoxic and normoxic cells is approximately 2:10 and that between hypoxic (0.5% O(2)) and normoxic cells is approximately 1:2.5, depending on the cell line. These ratios generally decrease at longer times. The (64)Cu-ATSM compound was found to be metabolized during incubation in a manner dependent on oxygenation conditions. Within 2 h under anoxic conditions, (64)Cu-ATSM could no longer be detected, although 60-90% of the amount of (64)Cu added as (64)Cu-ATSM was present in the medium. Non-ATSM (64)Cu was taken up by the cells, albeit at a much slower rate. Efflux rates of (64)Cu were found to be cell line dependent and appeared to be inversely correlated with the final (64)Cu uptake levels under anoxic conditions. CONCLUSION: The uptake and retention of (64)Cu and their relation to oxygenation conditions were found to be cell line dependent. Given the complexities in the oxygen dependence and cell line-dependent kinetics of uptake and retention of Cu following exposure to Cu-ATSM, the clinical utility of this compound may be disease site specific. |
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Authors:
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Paul Burgman; Joseph A O'Donoghue; Jason S Lewis; Michael J Welch; John L Humm; C Clifton Ling |
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Publication Detail:
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Type: Comparative Study; Journal Article; Research Support, N.I.H., Extramural; Research Support, U.S. Gov't, P.H.S. |
Journal Detail:
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Title: Nuclear medicine and biology Volume: 32 ISSN: 0969-8051 ISO Abbreviation: Nucl. Med. Biol. Publication Date: 2005 Aug |
Date Detail:
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Created Date: 2005-07-19 Completed Date: 2006-01-04 Revised Date: 2007-11-14 |
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: 623-30 Citation Subset: IM |
Affiliation:
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Department of Medical Physics, Memorial Sloan-Kettering Cancer Center, New York, NY 10021, USA. burgmanp@mskcc.org |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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Animals Cell Hypoxia* Copper / metabolism* Copper Radioisotopes / diagnostic use, pharmacokinetics* Female Humans Neoplasms / metabolism*, radionuclide imaging Organometallic Compounds / diagnostic use, pharmacokinetics* Oxygen / metabolism* Rats Thiosemicarbazones / diagnostic use, pharmacokinetics* Tissue Distribution Tumor Cells, Cultured |
| Grant Support | |
ID/Acronym/Agency:
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R01 CA84596/CA/NCI NIH HHS; R24 CA86307/CA/NCI NIH HHS |
| Chemical | |
Reg. No./Substance:
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0/Copper Radioisotopes; 0/Organometallic Compounds; 0/Thiosemicarbazones; 0/copper (II) diacetyl-di(N(4)-methylthiosemicarbazone); 7440-50-8/Copper; 7782-44-7/Oxygen |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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