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Am J Physiol Lung Cell Mol Physiol (June 24, 2005). doi:10.1152/ajplung.00146.2005
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Submitted on April 1, 2005
Accepted on June 17, 2005

Molecular imaging of lung glucose uptake after endotoxin in mice

Zhaohui Zhou1, James Kozlowksi1, Andrea L Goodrich1, Nathaniel Markman1, Delphine L Chen1, and Daniel P Schuster1*

1 Department of Internal Medicine and Radiology, Washington University School of Medicine and the Mallinckrodt Institute of Radiology, St. Louis, MO, USA

* To whom correspondence should be addressed. E-mail: daniel.schuster{at}wustl.edu.

Positron emission tomographic (PET) imaging after administration of the glucose analog fluorine-18 fluorodeoxyglucose ([18F]FDG) may be a useful way to study neutrophilic inflammation of the lungs. In this study, we sought to determine the specificity of the increase in lung [18F]FDG uptake after intraperitoneal endotoxin (Etx) for neutrophil influx into mouse lungs, and to determine the regulation of glucose uptake after Etx by Toll-like receptors (TLRs) and tumor necrosis factor-alpha (TNF{alpha}). Lung tissue radioactivity measurements by imaging were validated against counts in a gamma well counter. Glucose uptake was quantified as the [18F]FDG tissue-to-blood radioactivity ratio (TBR) after validating this measure against the gold standard measure of glucose uptake, the "net influx rate constant" (Ki). TBR measurements were made in a control group (no intervention), a group administered Etx, and a group administered Etx plus an additional agent (e.g., vinblastine) or Etx administered to a mutant mouse strain. The glucose uptake measurements were compared to measurements of myeloperoxidase (MPO). Increases in TBR after Etx were significantly but not completely eliminated by neutrophil depletion with vinblastine. The increases in TBR after Etx were consistent with signaling via either TLR-4 or TLR-2 (the latter probably secondary to peptidoglycan contaminants in the Etx preparation), and were decreased by drug inhibition of TLR-4 but not by inhibition of TNF{alpha} . Thus, molecular imaging can be used to non-invaseively monitor the biologic effects of Etx on the lungs in mice, and changes in lung glucose uptake can be used to monitor the effects of anti-inflammatory agents. Such imaging capacity provides a powerful new paradigm for translational "mouse-to-man" pulmonary research.




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