Document Detail

Cellular uptake of PET tracers of glucose metabolism and hypoxia and their linkage.
MedLine Citation:
PMID:  18682937     Owner:  NLM     Status:  MEDLINE    
PURPOSE: Tumour hypoxia and elevated glycolysis (Warburg effect) predict poor prognosis. Each parameter is assessable separately with positron emission tomography, but they are linked through anaerobic glycolysis (Pasteur effect). Here, we compare the oxygenation-dependent retention of fluoroazomycin arabinoside ([(18)F]FAZA), a promising but not well-characterised hypoxia-specific tracer, and fluorodeoxyglucose ([(18)F]FDG) in four carcinoma cell lines. METHODS: Cells seeded on coverslips were positioned in modified Petri dishes that allow physically separated cells to share the same tracer-containing medium pool. Following oxic, hypoxic or anoxic tracer incubation, coverslips were analysed for radioactivity ([(18)F]FDG + [(18)F]FAZA) or re-incubated in tracer-free oxygenated medium and then measured ([(18)F]FAZA). Next, we tested the reliability of [(18)F]FDG as a relative measure of glucose metabolic rate. Finally, from two cell lines, xenografts were established in mice, and the tracer distribution between hypoxic and well-oxygenated areas were deduced from tissue sections. RESULTS: Three hours of anoxia strongly stimulated [(18)F]FAZA retention with anoxic-to-oxic uptake ratios typically above 30. Three out of four cell lines displayed similar selectivity of [(18)F]FDG versus glucose, but oxic uptake and anoxic-to-oxic uptake ratio of [(18)F]FDG varied considerably. Although less pronounced, [(18)F]FAZA also showed superior in vivo hypoxia specificity compared with [(18)F]FDG. CONCLUSIONS: [(18)F]FAZA displays excellent in vitro characteristics for hypoxia imaging including modest cell-to-cell line variability and no binding in oxic cells. In contrast, the usability of [(18)F]FDG as a surrogate marker for hypoxia is questionable due to large variations in baseline (oxic) glucose metabolism and magnitudes of the Pasteur effects.
Morten Busk; Michael R Horsman; Steen Jakobsen; Johan Bussink; Albert van der Kogel; Jens Overgaard
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2008-08-06
Journal Detail:
Title:  European journal of nuclear medicine and molecular imaging     Volume:  35     ISSN:  1619-7089     ISO Abbreviation:  Eur. J. Nucl. Med. Mol. Imaging     Publication Date:  2008 Dec 
Date Detail:
Created Date:  2008-12-16     Completed Date:  2009-03-09     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  101140988     Medline TA:  Eur J Nucl Med Mol Imaging     Country:  Germany    
Other Details:
Languages:  eng     Pagination:  2294-303     Citation Subset:  IM    
Department of Experimental Clinical Oncology, Aarhus University Hospital, Aarhus C, Denmark.
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MeSH Terms
Anoxia / metabolism*,  pathology,  radionuclide imaging*
Binding, Competitive
Biological Transport
Cell Count
Cell Line, Tumor
Fluorodeoxyglucose F18 / diagnostic use,  metabolism
Glucose / metabolism*
Neoplasms / metabolism,  pathology
Nitroimidazoles / diagnostic use*,  metabolism*
Oxygen / metabolism
Positron-Emission Tomography
Time Factors
Reg. No./Substance:
0/Nitroimidazoles; 0/fluoroazomycin arabinoside; 50-99-7/Glucose; 63503-12-8/Fluorodeoxyglucose F18; 7782-44-7/Oxygen

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