title: Assessing lung inflammation after nanoparticle inhalation using 2-deoxy-2-[18F]fluoro-D-glucose positron emission tomography imaging.
abstract: OBJECTIVE
  The aim of the present study was to evaluate the use of 2-deoxy-2-[(18)F]fluoro-D-glucose ([(18)F]FDG) as a noninvasive strategy to assess the time course of inflammatory processes after inhalation of ZnO nanoparticles (NPs) in rats.
  
  
  METHODS
  Healthy, male Sprague-Dawley rats (n = 30) were divided in two groups of 15 animals each. Animals from one group (n = 15) were submitted to ZnO NPs inhalation in a chamber (10 nm to 4 μm particle size; maximum in number concentration, ∼ 200 nm; concentration = 245 mg/m(3)). Animals from the other group (n = 15, sham group) were also exposed following the same procedure, but no NPs were introduced into the chamber. Six animals per group were submitted to [(18)F]FDG-positron emission tomography (PET) studies at days 1, 7, and 28 after exposition, and the [(18)F]FDG influx constant (K i ) for the lungs was calculated using Patlak graphical analysis and an image derived blood input function. Nine animals per group were killed at 1, 7 and 28 days after exposure (n = 3 per group and time point), and the lungs were harvested and submitted to immunohistochemical and histological analysis.
  
  
  RESULTS
  Significantly higher mean whole-lung K i values were obtained for animals exposed to NPs at days 1 and 7 after exposure (0.0045 ± 0.0016 min(-1) and 0.0047 ± 0.0015 min(-1), respectively) compared to controls (0.0024 ± 0.0010 min(-1) and 0.0019 ± 0.0011 min(-1) at 1 and 7 days, respectively). The K i value for exposed animals dropped to 0.0023 ± 0.0010 min(-1) at day 28. This value was not significantly different from the values obtained at 1, 7, and 28 days for the control group. Immunofluorescence staining on lung tissue slices from animals exposed to ZnO NPs showed an increase in CD11b reactivity at days 1 and 7, followed by a decrease in CD11b positive cells at 28 days. Hematoxylin-eosin staining showed histological alterations in the exposed lungs to ZnO NPs at days 1 and 7 that recovered at 28 days postexposure.
  
  
  CONCLUSIONS
  The [(18)F]FDG influx rate constant (K i ) could be determined by PET using Patlak analysis and a corrected image derived input function. Higher K i values were obtained for animals exposed to ZnO NPs at days 1 and 7 after exposition. These results were in good concordance with immunohistochemical assays performed on harvested tissue samples.
authors.affiliation: Radiochemistry Department, Molecular Imaging Unit, CIC biomaGUNE, San Sebastian, Spain.
authors.forename: Carlos
authors.initials: C
authors.lastname: Pérez-Campaña
authors.forename: Vanessa
authors.initials: V
authors.lastname: Gómez-Vallejo
authors.forename: Maria
authors.initials: M
authors.lastname: Puigivila
authors.forename: Abraham
authors.initials: A
authors.lastname: Martin
authors.forename: Teresa
authors.initials: T
authors.lastname: Calvo-Fernández
authors.forename: Sergio E
authors.initials: SE
authors.lastname: Moya
authors.forename: Søren Thor
authors.initials: ST
authors.lastname: Larsen
authors.forename: Juan D
authors.initials: JD
authors.lastname: Gispert
authors.forename: Jordi
authors.initials: J
authors.lastname: Llop
mesh_terms: D000280:Administration, Inhalation; D000818:Animals; D019788:Fluorodeoxyglucose F18; D007150:Immunohistochemistry; D008168:Lung / Q000000981:diagnostic imaging / Q000473:pathology; D008297:Male; D053758:Nanoparticles / Q000008:administration & dosage* / Q000648:ultrastructure; D011014:Pneumonia / Q000000981:diagnostic imaging* / Q000473:pathology; D049268:Positron-Emission Tomography; D051381:Rats; D017207:Rats, Sprague-Dawley; D014057:Tomography, X-Ray Computed
chemical_list: D019788:Fluorodeoxyglucose F18