title: PET/CT with 18F-FDG- and 18F-FBEM-labeled leukocytes for metabolic activity and leukocyte recruitment monitoring in a mouse model of pulmonary fibrosis.
abstract: Idiopathic pulmonary fibrosis is characterized by a progressive and irreversible respiratory failure. Validated noninvasive methods able to assess disease activity are essential for prognostic purposes as well as for the evaluation of emerging antifibrotic treatments.
  
  
  METHODS
  C57BL/6 mice were used in a murine model of pulmonary fibrosis induced by an intratracheal instillation of bleomycin (control mice were instilled with a saline solution). At different times after instillation, PET/CT with (18)F-FDG- or (18)F-4-fluorobenzamido-N-ethylamino-maleimide ((18)F-FBEM)-labeled leukocytes was performed to assess metabolic activity and leukocyte recruitment, respectively.
  
  
  RESULTS
  In bleomycin-treated mice, a higher metabolic activity was measured on (18)F-FDG PET/CT scans from day 7 to day 24 after instillation, with a peak of activity measured at day 14. Of note, lung mean standardized uptake values correlated with bleomycin doses, histologic score of fibrosis, lung hydroxyproline content, and weight loss. Moreover, during the inflammatory phase of the model (day 7), but not the fibrotic phase (day 23), bleomycin-treated mice presented with an enhanced leukocyte recruitment as assessed by (18)F-FBEM-labeled leukocyte PET/CT. Autoradiographic analysis of lung sections and CD45 immunostaining confirm the higher and early recruitment of leukocytes in bleomycin-treated mice, compared with control mice.
  
  
  CONCLUSIONS
  (18)F-FDG- and (18)F-FBEM-labeled leukocyte PET/CT enable monitoring of metabolic activity and leukocyte recruitment in a mouse model of pulmonary fibrosis. Implications for preclinical evaluation of antifibrotic therapy are expected.
authors.affiliation: Service de Pneumologie, Hôpital Erasme, Université Libre de Bruxelles, Brussels, Belgium Institut de Recherche Interdisciplinaire en Biologie Humaine et Moléculaire (I.R.I.B.H.M.), Université Libre de Bruxelles, Brussels, Belgium bbondue@ulb.ac.be.
authors.forename: Benjamin
authors.initials: B
authors.lastname: Bondue
authors.affiliation: Center for Microscopy and Molecular Imaging, Université Libre de Bruxelles, Gosselies, Belgium Service de Médecine Nucléaire, Hôpital Erasme, Université Libre de Bruxelles, Brussels, Belgium; and.
authors.forename: Félicie
authors.initials: F
authors.lastname: Sherer
authors.affiliation: Center for Microscopy and Molecular Imaging, Université Libre de Bruxelles, Gosselies, Belgium Service de Médecine Nucléaire, Hôpital Erasme, Université Libre de Bruxelles, Brussels, Belgium; and.
authors.forename: Gaetan
authors.initials: G
authors.lastname: Van Simaeys
authors.affiliation: Center for Microscopy and Molecular Imaging, Université Libre de Bruxelles, Gosselies, Belgium Service de Médecine Nucléaire, Hôpital Erasme, Université Libre de Bruxelles, Brussels, Belgium; and.
authors.forename: Gilles
authors.initials: G
authors.lastname: Doumont
authors.affiliation: Center for Microscopy and Molecular Imaging, Université Libre de Bruxelles, Gosselies, Belgium Service de Médecine Nucléaire, Hôpital Erasme, Université Libre de Bruxelles, Brussels, Belgium; and.
authors.forename: Dominique
authors.initials: D
authors.lastname: Egrise
authors.affiliation: Centre for Toxicology and Applied Pharmacology, Université Catholique de Louvain, Louvain-la-Neuve, Belgium.
authors.forename: Yousof
authors.initials: Y
authors.lastname: Yakoub
authors.affiliation: Centre for Toxicology and Applied Pharmacology, Université Catholique de Louvain, Louvain-la-Neuve, Belgium.
authors.forename: François
authors.initials: F
authors.lastname: Huaux
authors.affiliation: Institut de Recherche Interdisciplinaire en Biologie Humaine et Moléculaire (I.R.I.B.H.M.), Université Libre de Bruxelles, Brussels, Belgium.
authors.forename: Marc
authors.initials: M
authors.lastname: Parmentier
authors.affiliation: Center for Microscopy and Molecular Imaging, Université Libre de Bruxelles, Gosselies, Belgium.
authors.forename: Sandrine
authors.initials: S
authors.lastname: Rorive
authors.affiliation: Center for Microscopy and Molecular Imaging, Université Libre de Bruxelles, Gosselies, Belgium.
authors.forename: Sébastien
authors.initials: S
authors.lastname: Sauvage
authors.affiliation: Center for Microscopy and Molecular Imaging, Université Libre de Bruxelles, Gosselies, Belgium Service de Médecine Nucléaire, Hôpital Erasme, Université Libre de Bruxelles, Brussels, Belgium; and.
authors.forename: Simon
authors.initials: S
authors.lastname: Lacroix
authors.affiliation: Institut de Recherche Interdisciplinaire en Biologie Humaine et Moléculaire (I.R.I.B.H.M.), Université Libre de Bruxelles, Brussels, Belgium.
authors.forename: Olivier
authors.initials: O
authors.lastname: Vosters
authors.affiliation: Service de Pneumologie, Hôpital Erasme, Université Libre de Bruxelles, Brussels, Belgium.
authors.forename: Paul
authors.initials: P
authors.lastname: De Vuyst
authors.affiliation: Center for Microscopy and Molecular Imaging, Université Libre de Bruxelles, Gosselies, Belgium Service de Médecine Nucléaire, Hôpital Erasme, Université Libre de Bruxelles, Brussels, Belgium; and.
authors.forename: Serge
authors.initials: S
authors.lastname: Goldman
mesh_terms: D000818:Animals; D001692:Biological Transport / Q000187:drug effects; D001761:Bleomycin / Q000009:adverse effects; D001835:Body Weight / Q000187:drug effects; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D005260:Female; D005355:Fibrosis; D019788:Fluorodeoxyglucose F18 / Q000378:metabolism; D007962:Leukocytes / Q000000981:diagnostic imaging / Q000276:immunology* / Q000378:metabolism*; D008168:Lung / Q000187:drug effects / Q000276:immunology; D008301:Maleimides / Q000378:metabolism; D051379:Mice; D049268:Positron-Emission Tomography; D011658:Pulmonary Fibrosis / Q000000981:diagnostic imaging / Q000378:metabolism* / Q000473:pathology; D013194:Staining and Labeling; D014057:Tomography, X-Ray Computed
chemical_list: D008301:Maleimides; C512447:N-(2-(4-18F-fluorobenzamido)ethyl)maleimide; D019788:Fluorodeoxyglucose F18; D001761:Bleomycin
keywords: PET scan; bleomycin; disease monitoring; fluorodeoxyglucose; pulmonary fibrosis