Benjamin Bondue1, Félicie Sherer2, Gaetan Van Simaeys2, Gilles Doumont2, Dominique Egrise2, Yousof Yakoub3, François Huaux3, Marc Parmentier4, Sandrine Rorive5, Sébastien Sauvage5, Simon Lacroix2, Olivier Vosters4, Paul De Vuyst6, Serge Goldman2. 1. 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. 2. 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. 3. Centre for Toxicology and Applied Pharmacology, Université Catholique de Louvain, Louvain-la-Neuve, Belgium. 4. Institut de Recherche Interdisciplinaire en Biologie Humaine et Moléculaire (I.R.I.B.H.M.), Université Libre de Bruxelles, Brussels, Belgium. 5. Center for Microscopy and Molecular Imaging, Université Libre de Bruxelles, Gosselies, Belgium. 6. Service de Pneumologie, Hôpital Erasme, Université Libre de Bruxelles, Brussels, Belgium.
Abstract
UNLABELLED: 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. CONCLUSION: (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.
UNLABELLED: 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. CONCLUSION: (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.
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