PET/CT with 18F-FDG– and 18F-FBEM–Labeled Leukocytes for Metabolic Activity and Leukocyte Recruitment Monitoring in a Mouse Model of Pulmonary Fibrosis

Journal of Nuclear Medicine

Benjamin Bondue¹  Olivier Vosters¹  Gilles Doumont¹  Gaetan Van Simaeys¹  Marc Parmentier¹  Yousof Yakoub¹  Sandrine Rorive¹  Sébastien Sauvage¹  Paul De Vuyst¹  Dominique Egrise¹  Simon Lacroix¹  Félicie Sherer¹  François Huaux¹  Serge Goldman¹ 

关键词: pulmonary fibrosis;    bleomycin;    PET scan;    fluorodeoxyglucose;    disease monitoring;   

DOI  :  10.2967/jnumed.114.147421

学科分类：医学（综合）

来源: Society of Nuclear Medicine

【 摘 要 】

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 18F-FDG– or 18F-4-fluorobenzamido-N-ethylamino-maleimide (18F-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 18F-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 18F-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: 18F-FDG– and 18F-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.

【 授权许可】

Unknown