Absence of early metabolic response assessed by 18F-FDG PET/CT after initiation of antifibrotic drugs in IPF patients.
Aged
Animals
Antineoplastic Agents
/ therapeutic use
Female
Fibrosis
Fluorodeoxyglucose F18
Humans
Idiopathic Pulmonary Fibrosis
/ diagnostic imaging
Indoles
/ therapeutic use
Male
Mice
Mice, Inbred C57BL
Middle Aged
Positron Emission Tomography Computed Tomography
/ methods
Prospective Studies
Pyridones
/ therapeutic use
Biomarker
ILD
IPF
Idiopathic pulmonary fibrosis
Interstitial lung disease
Nintedanib
PET/CT
Pirfenidone
Journal
Respiratory research
ISSN: 1465-993X
Titre abrégé: Respir Res
Pays: England
ID NLM: 101090633
Informations de publication
Date de publication:
15 Jan 2019
15 Jan 2019
Historique:
received:
05
10
2018
accepted:
02
01
2019
entrez:
17
1
2019
pubmed:
17
1
2019
medline:
12
3
2019
Statut:
epublish
Résumé
Idiopathic pulmonary fibrosis (IPF) is characterized by a progressive and irreversible respiratory failure. Non-invasive markers of disease activity are essential for prognosis and evaluation of early response to anti-fibrotic treatments. The aims of this study were to determine whether fluorodeoxyglucose ([18F]-FDG) lung uptake is reduced after initiation of pirfenidone or nintedanib and to assess its possible use as a prognostic factor. [18F]-FDG PET/CT was performed in IPF patients and in a murine model of pulmonary fibrosis. PET/CTs were performed at day 8 and day 15 post-instillation of bleomycin in pirfenidone- or vehicule-treated mice. In IPF patients, PET-CT was performed before and 3 months after the initiation of pirfenidone or nintedanib. In bleomycin-treated mice, pirfenidone significantly reduced the [18F]-FDG uptake compared to vehicule-treated mice at day 15 (p < 0.001), whereas no difference was observed at day 8 after bleomycin administration. In IPF patients, [18F]-FDG lung uptake before and after 3 months of treatment by nintedanib (n = 11) or pirfenidone (n = 14) showed no significant difference regardless the antifibrotic treatment. Moreover, no difference was noticed between patients with progressive or non-progressive disease at one year of follow up. Pirfenidone significantly reduces the lung [18F]-FDG uptake during the fibrotic phase in a mouse model of IPF. However, these preclinical data were not confirmed in IPF patients 3 months after the initiation of antifibrotic therapy. [18F]-FDG seems therefore not useful in clinical practice to assess the early response of IPF patients to nintedanib or pirfenidone.
Sections du résumé
BACKGROUND
BACKGROUND
Idiopathic pulmonary fibrosis (IPF) is characterized by a progressive and irreversible respiratory failure. Non-invasive markers of disease activity are essential for prognosis and evaluation of early response to anti-fibrotic treatments.
OBJECTIVES
OBJECTIVE
The aims of this study were to determine whether fluorodeoxyglucose ([18F]-FDG) lung uptake is reduced after initiation of pirfenidone or nintedanib and to assess its possible use as a prognostic factor.
METHODS
METHODS
[18F]-FDG PET/CT was performed in IPF patients and in a murine model of pulmonary fibrosis. PET/CTs were performed at day 8 and day 15 post-instillation of bleomycin in pirfenidone- or vehicule-treated mice. In IPF patients, PET-CT was performed before and 3 months after the initiation of pirfenidone or nintedanib.
RESULTS
RESULTS
In bleomycin-treated mice, pirfenidone significantly reduced the [18F]-FDG uptake compared to vehicule-treated mice at day 15 (p < 0.001), whereas no difference was observed at day 8 after bleomycin administration. In IPF patients, [18F]-FDG lung uptake before and after 3 months of treatment by nintedanib (n = 11) or pirfenidone (n = 14) showed no significant difference regardless the antifibrotic treatment. Moreover, no difference was noticed between patients with progressive or non-progressive disease at one year of follow up.
CONCLUSIONS
CONCLUSIONS
Pirfenidone significantly reduces the lung [18F]-FDG uptake during the fibrotic phase in a mouse model of IPF. However, these preclinical data were not confirmed in IPF patients 3 months after the initiation of antifibrotic therapy. [18F]-FDG seems therefore not useful in clinical practice to assess the early response of IPF patients to nintedanib or pirfenidone.
Identifiants
pubmed: 30646908
doi: 10.1186/s12931-019-0974-5
pii: 10.1186/s12931-019-0974-5
pmc: PMC6334423
doi:
Substances chimiques
Antineoplastic Agents
0
Indoles
0
Pyridones
0
Fluorodeoxyglucose F18
0Z5B2CJX4D
pirfenidone
D7NLD2JX7U
nintedanib
G6HRD2P839
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
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