Document Detail


Pharmacologic Activation of Tumor Hypoxia: A Means to Increase Tumor 2-Deoxy-2-[18F]Fluoro-D-glucose Uptake?
MedLine Citation:
PMID:  23348791     Owner:  NLM     Status:  In-Data-Review    
Abstract/OtherAbstract:
AbstractTumor hypoxia and tumor metabolism are linked through the activation of metabolic genes following hypoxia-inducible factor 1 (HIF-1) activation. This raises the question of whether this relationship can be exploited to improve 2-deoxy-2-[18F]fluoro-d-glucose positron emission tomography ([18F]FDG-PET). To do this, [18F]FDG uptake was investigated after chemical induction of hypoxia and chemical activation of HIF-1 in an in vitro and an in vivo model of a human colorectal carcinoma. [18F]FDG uptake, HIF-1α protein levels, and messenger ribonucleic acid expression of glucose transporter 1 (GLUT1), hexokinase 2, HIF-1α, and carbonic anhydrase IX (CA IX) were determined in HT29 cells after treatment with 200 μM CoCl2 and 500 μM dimethyloxalylglycine (DMOG). In an HT29 xenograft, the distribution of endogenous and exogenous markers of hypoxia was investigated using immunohistochemistry, and tumor [18F]FDG uptake was determined after treatment with a single dose of 5 mg/kg hydralazine and 8 mg DMOG. Treatment of HT29 cells with CoCl2 and DMOG induced functional HIF-1 and resulted in increased [18F]FDG uptake. In an HT29 xenograft, a similar spatial distribution of pimonidazole, CA IX, and GLUT1 was found, and treatment with DMOG resulted in significant increases in maximum and mean standardized uptake values using [18F]FDG-PET. Chemical activation of HIF-1 can increase in vitro and in vivo [18F]FDG uptake. Imaging after pharmacologic HIF-1 activation might increase tumor [18F]FDG uptake when using [18F]FDG-PET.
Authors:
Gilles Mees; Rudi Dierckx; Christel Vangestel; Debby Laukens; Nancy Van Damme; Christophe Van de Wiele
Publication Detail:
Type:  Journal Article    
Journal Detail:
Title:  Molecular imaging     Volume:  12     ISSN:  1536-0121     ISO Abbreviation:  Mol Imaging     Publication Date:  2013 Feb 
Date Detail:
Created Date:  2013-01-25     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  101120118     Medline TA:  Mol Imaging     Country:  United States    
Other Details:
Languages:  eng     Pagination:  49-58     Citation Subset:  IM    
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