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European Journal of Nuclear Medicine and Molecular Imaging

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Open Access 01-09-2021 | Idiopathic Pulmonary Fibrosis | Original Article

[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

Authors: Julie Tanguy, Françoise Goirand, Alexanne Bouchard, Jame Frenay, Mathieu Moreau, Céline Mothes, Alexandra Oudot, Alex Helbling, Mélanie Guillemin, Philippe Bonniaud, Alexandre Cochet, Bertrand Collin, Pierre-Simon Bellaye

Published in: European Journal of Nuclear Medicine and Molecular Imaging | Issue 10/2021

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 [¹⁸F]FMISO as a predictive biomarker of disease progression and therapy efficacy in preclinical models of lung fibrosis in comparison with [¹⁸F]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 [¹⁸F]FDG and [¹⁸F]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 [¹⁸F]FDG and [¹⁸F]FMISO uptakes are upregulated in established lung fibrosis (1.4-, 2.6- and 3.2-fold increase respectively). At early stages, lung areas with [¹⁸F]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 [¹⁸F]FDG and [¹⁸F]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 [¹⁸F]FMISO lung uptake was correlated with aggressive disease progression and better nintedanib efficacy.

Conclusion

[¹⁸F]FMISO PET imaging is a promising tool to early detect and monitor lung fibrosis progression and therapy efficacy.

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Title: [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
Authors: Julie Tanguy
Françoise Goirand
Alexanne Bouchard
Jame Frenay
Mathieu Moreau
Céline Mothes
Alexandra Oudot
Alex Helbling
Mélanie Guillemin
Philippe Bonniaud
Alexandre Cochet
Bertrand Collin
Pierre-Simon Bellaye
Publication date: 01-09-2021
Publisher: Springer Berlin Heidelberg
Keywords: Idiopathic Pulmonary Fibrosis
Computed Tomography
Computed Tomography
Nintedanib
Biomarkers
Published in: European Journal of Nuclear Medicine and Molecular Imaging / Issue 10/2021
Print ISSN: 1619-7070
Electronic ISSN: 1619-7089
DOI: https://doi.org/10.1007/s00259-021-05209-2

Keynote webinar | Spotlight on medication adherence

Springer Medicine

[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

Abstract

Purpose

Methods

Results

Conclusion

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Abstract

Purpose

Methods

Results

Conclusion

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