title: Imaging pulmonary inducible nitric oxide synthase expression with PET.
abstract: Inducible nitric oxide synthase (iNOS) activity increases in acute and chronic inflammatory lung diseases. Imaging iNOS expression may be useful as an inflammation biomarker for monitoring lung disease activity. We developed a novel tracer for PET that binds to iNOS in vivo, (18)F-NOS. In this study, we tested whether (18)F-NOS could quantify iNOS expression from endotoxin-induced lung inflammation in healthy volunteers.
  
  
  METHODS
  Healthy volunteers were screened to exclude cardiopulmonary disease. Qualifying volunteers underwent a baseline, 1-h dynamic (18)F-NOS PET/CT scan. Endotoxin (4 ng/kg) was then instilled bronchoscopically in the right middle lobe. (18)F-NOS imaging was performed again approximately 16 h after endotoxin instillation. Radiolabeled metabolites were determined from blood samples. Cells recovered by bronchoalveolar lavage (BAL) after imaging were stained immunohistochemically for iNOS. (18)F-NOS uptake was quantified as the distribution volume ratio (DVR) determined by Logan plot graphical analysis in volumes of interest placed over the area of endotoxin instillation and in an equivalent lung region on the left. The mean Hounsfield units (HUs) were also computed using the same volumes of interest to measure density changes.
  
  
  RESULTS
  Seven healthy volunteers with normal pulmonary function completed the study with evaluable data. The DVR increased by approximately 30%, from a baseline mean of 0.42 ± 0.07 to 0.54 ± 0.12, and the mean HUs by 11% after endotoxin in 6 volunteers who had positive iNOS staining in BAL cells. The DVR did not change in the left lung after endotoxin. In 1 volunteer with low-level iNOS staining in BAL cells, the mean HUs increased by 7% without an increase in DVR. Metabolism was rapid, with approximately 50% of the parent compound at 5 min and 17% at 60 min after injection.
  
  
  CONCLUSIONS
  (18)F-NOS can be used to image iNOS activity in acute lung inflammation in humans and may be a useful PET tracer for imaging iNOS expression in inflammatory lung disease.
authors.affiliation: Division of Pulmonary and Critical Care Medicine, Department of Internal Medicine, Washington University School of Medicine, St. Louis, Missouri.
authors.forename: Howard J
authors.initials: HJ
authors.lastname: Huang
authors.affiliation: Division of Pulmonary and Critical Care Medicine, Department of Internal Medicine, Washington University School of Medicine, St. Louis, Missouri.
authors.forename: Warren
authors.initials: W
authors.lastname: Isakow
authors.affiliation: Division of Pulmonary and Critical Care Medicine, Department of Internal Medicine, Washington University School of Medicine, St. Louis, Missouri.
authors.forename: Derek E
authors.initials: DE
authors.lastname: Byers
authors.affiliation: Mallinckrodt Institute of Radiology, Washington University School of Medicine, St. Louis, Missouri.
authors.forename: Jacquelyn T
authors.initials: JT
authors.lastname: Engle
authors.affiliation: Mallinckrodt Institute of Radiology, Washington University School of Medicine, St. Louis, Missouri.
authors.forename: Elizabeth A
authors.initials: EA
authors.lastname: Griffin
authors.affiliation: Center for Clinical Studies, Department of Internal Medicine, Washington University School of Medicine, St. Louis, Missouri; and.
authors.forename: Debra
authors.initials: D
authors.lastname: Kemp
authors.affiliation: Division of Pulmonary and Critical Care Medicine, Department of Internal Medicine, Washington University School of Medicine, St. Louis, Missouri Mallinckrodt Institute of Radiology, Washington University School of Medicine, St. Louis, Missouri.
authors.forename: Steven L
authors.initials: SL
authors.lastname: Brody
authors.affiliation: Mallinckrodt Institute of Radiology, Washington University School of Medicine, St. Louis, Missouri.
authors.forename: Robert J
authors.initials: RJ
authors.lastname: Gropler
authors.affiliation: Division of Biostatistics, Washington University School of Medicine, St. Louis, Missouri.
authors.forename: J Philip
authors.initials: JP
authors.lastname: Miller
authors.affiliation: Mallinckrodt Institute of Radiology, Washington University School of Medicine, St. Louis, Missouri.
authors.forename: Wenhua
authors.initials: W
authors.lastname: Chu
authors.affiliation: Mallinckrodt Institute of Radiology, Washington University School of Medicine, St. Louis, Missouri.
authors.forename: Dong
authors.initials: D
authors.lastname: Zhou
authors.affiliation: Division of Pulmonary and Critical Care Medicine, Department of Internal Medicine, Washington University School of Medicine, St. Louis, Missouri.
authors.forename: Richard A
authors.initials: RA
authors.lastname: Pierce
authors.affiliation: Division of Pulmonary and Critical Care Medicine, Department of Internal Medicine, Washington University School of Medicine, St. Louis, Missouri.
authors.forename: Mario
authors.initials: M
authors.lastname: Castro
authors.affiliation: Mallinckrodt Institute of Radiology, Washington University School of Medicine, St. Louis, Missouri.
authors.forename: Robert H
authors.initials: RH
authors.lastname: Mach
authors.affiliation: Division of Pulmonary and Critical Care Medicine, Department of Internal Medicine, Washington University School of Medicine, St. Louis, Missouri Mallinckrodt Institute of Radiology, Washington University School of Medicine, St. Louis, Missouri chend@mir.wustl.edu.
authors.forename: Delphine L
authors.initials: DL
authors.lastname: Chen
mesh_terms: D000328:Adult; D001692:Biological Transport / Q000187:drug effects; D018893:Bronchoalveolar Lavage; D004731:Endotoxins / Q000633:toxicity; D005260:Female; D015971:Gene Expression Regulation, Enzymologic / Q000187:drug effects; D064368:Healthy Volunteers; D006801:Humans; D008168:Lung / Q000000981:diagnostic imaging* / Q000187:drug effects / Q000201:enzymology* / Q000378:metabolism; D008297:Male; D052247:Nitric Oxide Synthase Type II / Q000378:metabolism*; D049268:Positron-Emission Tomography; D019275:Radiopharmaceuticals / Q000097:blood / Q000378:metabolism
chemical_list: D004731:Endotoxins; D019275:Radiopharmaceuticals; D052247:Nitric Oxide Synthase Type II
keywords: endotoxin; inducible nitric oxide synthase; lung inflammation; positron emission tomography