title: 18F-fluoro-2-deoxyglucose PET informs neutrophil accumulation and activation in lipopolysaccharide-induced acute lung injury.
abstract: BACKGROUND
  Molecular imaging of the earliest events related to the development of acute lung injury (ALI)/acute respiratory distress syndrome (ARDS) could facilitate therapeutic development and patient management. We previously reported that18F-fluoro-2-deoxyglucose (18F-FDG) PET identifies ALI/ARDS prior to radiographic abnormalities. The purpose of this study was to establish the time courses of18F-FDG uptake, edema and neutrophil recruitment in an endotoxin-induced acute lung injury model and to examine molecular events required for14C-2DG uptake in activated neutrophils.
  
  
  METHODS
  Lung uptake of18F-FDG was measured by PET in control male Sprague Dawley rats and at 2, 6 and 24h following the intraperitoneal injection of 10mg/kg LPS. Lung edema (attenuation) was measured by microCT. Neutrophil influx into the lungs was measured by myeloperoxidase assay. Control and activated human donor neutrophils were compared for uptake of14C-2DG, transcription and content of hexokinase and GLUT isoforms and for hexokinase (HK) activity.
  
  
  RESULTS
  Significant uptake of18F-FDG occurred by 2h following LPS, and progressively increased to 24h. Lung uptake of18F-FDG preceded increased CT attenuation (lung edema). Myeloperoxidase activity in the lungs, supporting neutrophil influx, paralleled18F-FDG uptake. Activation of isolated human neutrophils resulted in increased uptake of14C-2DG, expression of GLUT 3 and GLUT 4 and expression and increased HK1 activity.
  
  
  CONCLUSIONS
  Systemic endotoxin-induced ALI results in very early and progressive uptake of18F-FDG, parallels neutrophil accumulation and occurs earlier than lung injury edema. Activated neutrophils show increased uptake of14C-2DG, expression of specific GLUT3, GLUT4 and HK1 protein and HK activity. ADVANCES IN KNOWLEDGE AND IMPLICATIONS FOR PATIENT CARE:18F-FDG pulmonary uptake is an early biomarker of neutrophil recruitment in ALI and is associated with specific molecular events that mediate14C-2DG uptake in activated neutrophils.18F-FDG PET may provide a potential mechanism for early diagnosis and therapeutic assessment of ALI/ARDS.
authors.affiliation: Department of Radiology, Federal University of Rio de Janeiro, Rio de Janeiro, Brazil.
authors.forename: Rosana S
authors.initials: RS
authors.lastname: Rodrigues
authors.affiliation: National Institute of Infectious Disease Evandro Chagas, Fundação Oswaldo Cruz, Rio de Janeiro, Rio de Janeiro, Brazil.
authors.forename: Fernando A
authors.initials: FA
authors.lastname: Bozza
authors.affiliation: Department of Radiology and Imaging Sciences, University of Utah School of Medicine, Salt Lake City, UT, USA.
authors.forename: Christopher J
authors.initials: CJ
authors.lastname: Hanrahan
authors.affiliation: Department of Radiology and Imaging Sciences, University of Utah School of Medicine, Salt Lake City, UT, USA.
authors.forename: Li-Ming
authors.initials: LM
authors.lastname: Wang
authors.affiliation: Department of Radiology and Imaging Sciences, University of Utah School of Medicine, Salt Lake City, UT, USA.
authors.forename: Qi
authors.initials: Q
authors.lastname: Wu
authors.affiliation: Department of Radiology and Imaging Sciences, University of Utah School of Medicine, Salt Lake City, UT, USA.
authors.forename: John M
authors.initials: JM
authors.lastname: Hoffman
authors.affiliation: Department of Internal Medicine, University of Utah School of Medicine, Salt Lake City, UT, USA.
authors.forename: Guy A
authors.initials: GA
authors.lastname: Zimmerman
authors.affiliation: Department of Radiology and Imaging Sciences, University of Utah School of Medicine, Salt Lake City, UT, USA. Electronic address: kathryn.morton@hsc.utah.edu.
authors.forename: Kathryn A
authors.initials: KA
authors.lastname: Morton
mesh_terms: D055371:Acute Lung Injury / Q000139:chemically induced / Q000000981:diagnostic imaging* / Q000276:immunology* / Q000378:metabolism; D000818:Animals; D001692:Biological Transport / Q000187:drug effects; D002462:Cell Membrane / Q000187:drug effects / Q000378:metabolism; D003600:Cytosol / Q000187:drug effects / Q000378:metabolism; D019788:Fluorodeoxyglucose F18 / Q000378:metabolism; D015971:Gene Expression Regulation, Enzymologic / Q000187:drug effects; D051246:Glucose Transport Proteins, Facilitative / Q000378:metabolism; D006593:Hexokinase / Q000378:metabolism; D008070:Lipopolysaccharides / Q000494:pharmacology*; D008168:Lung / Q000000981:diagnostic imaging / Q000187:drug effects / Q000276:immunology / Q000473:pathology; D008297:Male; D018375:Neutrophil Activation / Q000187:drug effects*; D009504:Neutrophils / Q000166:cytology / Q000187:drug effects* / Q000276:immunology; D049268:Positron-Emission Tomography; D051381:Rats; D017207:Rats, Sprague-Dawley; D012128:Respiratory Distress Syndrome / Q000139:chemically induced / Q000000981:diagnostic imaging / Q000276:immunology / Q000378:metabolism
chemical_list: D051246:Glucose Transport Proteins, Facilitative; D008070:Lipopolysaccharides; D019788:Fluorodeoxyglucose F18; D006593:Hexokinase
keywords: 18F-fluordeoxyglucose; ARDS; Acute lung injury; FDG; Lipopolysaccharide; Neutrophils