INTRODUCTION . Idiopathic pulmonary fibrosis is characterized by a progressive and irreversible respiratory failure. Non-invasive methods to assess disease activity are essential for prognostic purpose and for the evaluation of anti-fibrotic treatments. Therefore, we developed a murine model to explore PET techniques in lung fibrotic diseases. METHODS. C57Bl6 mice were used in a model of pulmonary fibrosis induced by an intra-tracheal instillation of bleomycin. At different times post-instillation, 18 F-FDG or 18 F-FBEM-labeled leukocytes PET-CT were 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 post-instillation with a peak of activity measured at day 14. Dose-response experiments demonstrated also a correlation between SUV and the dose of bleomycin administrated. Moreover, at day 7 and 14 post instillation — but not at day 24 —, bleomycin-treated mice present a higher leukocyte recruitment as assessed by 18 F-FBEM-labeled leukocyte PET-CT. These in vivo data are confirmed by autoradiographic analysis of lung sections performed at the selected times (for both 18 F-FDG or 18 F-FBEM-labeled leukocytes imaging), and by anti-CD45 staining of lung sections, showing higher leukocyte recruitment in bleomycin-treated mice compared to control mice. CONCLUSIONS. 18 F-FDG and 18 F-FBEM-labeled leukocytes PET-CT enable to monitor metabolic activity and leukocyte recruitment in a mouse model of pulmonary fibrosis. Implications for pre-clinical evaluation of anti-fibrotic therapies are expected.
Bondue et al. (Mon,) studied this question.