[18F]FMISO PET/CT imaging of hypoxia as a non-invasive biomarker of disease progression and therapy efficacy in a preclinical model of pulmonary fibrosis: comparison with the [18F]FDG PET/CT approach - Université de Bourgogne Accéder directement au contenu
Article Dans Une Revue European Journal of Nuclear Medicine and Molecular Imaging Année : 2021

[18F]FMISO PET/CT imaging of hypoxia as a non-invasive biomarker of disease progression and therapy efficacy in a preclinical model of pulmonary fibrosis: comparison with the [18F]FDG PET/CT approach

Julie Tanguy
  • Fonction : Auteur
Françoise Goirand
  • Fonction : Auteur
Alexanne Bouchard
  • Fonction : Auteur
Jame Frenay
  • Fonction : Auteur
Mathieu Moreau
Céline Mothes
  • Fonction : Auteur
Alexandra Oudot
Alex Helbling
  • Fonction : Auteur
Mélanie Guillemin
  • Fonction : Auteur
Philippe Bonniaud
Bertrand Collin
  • Fonction : Auteur
Pierre-Simon Bellaye

Résumé

Abstract Purpose Idiopathic pulmonary fibrosis (IPF) is a progressive disease with poor outcome and limited therapeutic options. Imaging of IPF is limited to high-resolution computed tomography (HRCT) which is often not sufficient for a definite diagnosis and has a limited impact on therapeutic decision and patient management. Hypoxia of the lung is a significant feature of IPF but its role on disease progression remains elusive. Thus, the aim of our study was to evaluate hypoxia imaging with [ 18 F]FMISO as a predictive biomarker of disease progression and therapy efficacy in preclinical models of lung fibrosis in comparison with [ 18 F]FDG. Methods Eight-week-old C57/BL6 mice received an intratracheal administration of bleomycin (BLM) at day (D) 0 to initiate lung fibrosis. Mice received pirfenidone (300 mg/kg) or nintedanib (60 mg/kg) by daily gavage from D9 to D23. Mice underwent successive PET/CT imaging at several stages of the disease (baseline, D8/D9, D15/D16, D22/D23) with [ 18 F]FDG and [ 18 F]FMISO. Histological determination of the lung expression of HIF-1α and GLUT-1 was performed at D23. Results We demonstrate that mean lung density on CT as well as [ 18 F]FDG and [ 18 F]FMISO uptakes are upregulated in established lung fibrosis (1.4-, 2.6- and 3.2-fold increase respectively). At early stages, lung areas with [ 18 F]FMISO uptake are still appearing normal on CT scans and correspond to areas which will deteriorate towards fibrotic lesions at later timepoints. Nintedanib and pirfenidone dramatically and rapidly decreased mean lung density on CT as well as [ 18 F]FDG and [ 18 F]FMISO lung uptakes (pirfenidone: 1.2-, 2.9- and 2.6-fold decrease; nintedanib: 1.2-, 2.3- and 2.5-fold decrease respectively). Early [ 18 F]FMISO lung uptake was correlated with aggressive disease progression and better nintedanib efficacy. Conclusion [ 18 F]FMISO PET imaging is a promising tool to early detect and monitor lung fibrosis progression and therapy efficacy.

Dates et versions

hal-03611646 , version 1 (17-03-2022)

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Citer

Julie Tanguy, Françoise Goirand, Alexanne Bouchard, Jame Frenay, Mathieu Moreau, et al.. [18F]FMISO PET/CT imaging of hypoxia as a non-invasive biomarker of disease progression and therapy efficacy in a preclinical model of pulmonary fibrosis: comparison with the [18F]FDG PET/CT approach. European Journal of Nuclear Medicine and Molecular Imaging, 2021, 48 (10), pp.3058-3074. ⟨10.1007/s00259-021-05209-2⟩. ⟨hal-03611646⟩
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