| Biodistribution of the nitroimidazole EF5 (2-[2-nitro-1H-imidazol-1-yl]-N-(2,2,3,3,3-pentafluoropropyl) acetamide) in mice bearing subcutaneous EMT6 tumors. | |
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MedLine Citation:
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PMID: 8627516 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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The characteristic reduction and binding of nitroimidazoles to cellular macromolecules in the absence of oxygen allows their use for detection and characterization of hypoxia. The biodistribution of a new nitroimidazole, EF5 (2-[2-nitro-1H-imidazol-1-yl]-N-(2,2,3,3,3-pentafluoropropyl) acetamide), in mice bearing EMT6 tumors is described. Detection methods based on radioactivity and monoclonal antibody techniques are compared for liver and tumor. All nonexcretory tissues demonstrated similar levels of radioactivity at 0.5 hr postinjection of drug, demonstrating equivalent access of EF5 to all tissues. At 24 hr, when unbound drug has been cleared, the tissues with the highest binding are the liver, esophagus, bladder and tumor. Typically, liver tissue contains the highest level of radioactivity at this time. Examination of tumor and liver tissue by use of fluorescence microscopy and Cy3-bound monoclonal antibodies specific for EF5 adducts showed that the patterns of binding in tumor are considerably more heterogeneous than those of liver. Histograms of fluorescence intensity, with use of these antibodies, demonstrate average and maximal binding higher in tumors than in the liver. This divergence from the radioactivity data was determined to be unrelated to sampling error, differential antibody access or staining efficiency of liver vs. tumor tissue. A possible cause is the scavenging of radioactive drug metabolites by liver. The data presented herein suggest that EF5 is useful as a hypoxia detector and that monoclonal antibody detection methods can give detailed information on the distribution of EF5 binding. This technology may allow an accurate estimation of the oxygenation and/or nitroreductase levels in both tumor and normal tissues. |
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Authors:
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K M Laughlin; S M Evans; W T Jenkins; M Tracy; C Y Chan; E M Lord; C J Koch |
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Publication Detail:
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Type: Journal Article; Research Support, Non-U.S. Gov't; Research Support, U.S. Gov't, P.H.S. |
Journal Detail:
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Title: The Journal of pharmacology and experimental therapeutics Volume: 277 ISSN: 0022-3565 ISO Abbreviation: J. Pharmacol. Exp. Ther. Publication Date: 1996 May |
Date Detail:
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Created Date: 1996-06-27 Completed Date: 1996-06-27 Revised Date: 2007-11-14 |
Medline Journal Info:
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Nlm Unique ID: 0376362 Medline TA: J Pharmacol Exp Ther Country: UNITED STATES |
Other Details:
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Languages: eng Pagination: 1049-57 Citation Subset: IM |
Affiliation:
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University of Pennsylvania, Department of Radiation Oncology, Philadelphia, USA. |
Export Citation:
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APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
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Animals Anoxia / diagnosis Antineoplastic Agents / pharmacokinetics* Etanidazole / analogs & derivatives*, pharmacokinetics Hydrocarbons, Fluorinated / pharmacokinetics* Mice Mice, Inbred BALB C Neoplasms, Experimental / metabolism* Oxygen / metabolism Tissue Distribution |
| Grant Support | |
ID/Acronym/Agency:
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CA-56679-01A1/CA/NCI NIH HHS |
| Chemical | |
Reg. No./Substance:
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0/2-(2-nitro-1H-imidazol-1-yl)-N-(2,2,3,3,3-pentafluoropropyl)acetamide; 0/Antineoplastic Agents; 0/Hydrocarbons, Fluorinated; 22668-01-5/Etanidazole; 7782-44-7/Oxygen |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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