| الوصف: |
Background: Interstitial lung disease (ILD) is the most common cause of death in systemic sclerosis (SSc). However, the course of ILD in this population is highly variable. Effective diagnostic tools to assess activity and to predict the individual course of the disease are lacking. Here, we tested the hypothesis that in vivo quantification of fibroblast activation may correlate with ILD activity and improve risk stratification in SSc patients. Methods: Fibroblast activation was visualized by positron emission tomography/computed tomography (PET/CT) using the 68Gallium-labeled selective inhibitor of fibroblast activation protein (68Ga-FAPI-04). We correlated 68Ga-FAPI-04 uptake with changes in lung function parameters, high resolution CT scan (HRCT) and patient reported outcomes. 68Ga-FAPI-04 PET/CTs, HRCTs and lung function tests were evaluated in a blinded manner. Findings: In this single center study, we enrolled 21 patients with SSc-ILD, five patients with dermatomyositis-associated-ILD, ten non-SSc/non-ILD control patients and ten non-diseased control individuals. 68Ga-FAPI-04 accumulated in fibrotic areas of the lungs in SSc-ILD with significantly higher wlSUVmean (p 1.0 or a wlTL-FAPI > 500 cm3 demonstrated radiologic progression and decline of FVC after 6 months, but none of the patients with less 68Ga-FAPI-04 accumulation. In consecutive 68Ga-FAPI-04-PET/CTs, changes in 68Ga-FAPI-04 uptake correlated with response to the fibroblast-targeting antifibrotic agent nintedanib. Interpretation: Our study presents first in human evidence that fibroblast activation correlates with fibrotic activity and disease progression in the lungs of SSc-ILD patients and that 68Ga-FAPI-04-PET/CT may improve risk stratification. Funding: German Research Foundation, ELAN-Foundation-Erlangen and Bundesministerium fur Bildung und Forschung. Conflict of Interest: O.D. has consulted for, or has received research funding from, 4D Science, Actelion, Active Biotech, Bayer-Schering, Biogen, Biovitrium, BMS, Boehringer, EpiPharm, Ergonex, GSK, Inventiva, Medac, Novartis, Pfizer, Roche/Genentech, Sanofi/Genzyme, Serodapharm, Sinoxa and United BioSource Corporation; JHWD has consultancy relationships and/or has received research funding from Actelion, BMS, Celgene, Bayer Pharma, Boehringer Ingelheim, JBTherapeutics, Sanofi-Aventis, Novartis, UCB, GSK, Array Biopharma, Galapagos, Inventiva and Active Biotech in the area of potential treatments of SSc and is stock owner of 4D Science. Ethical Approval: File number 30_19B, Ethics Committee Friedrich-Alexander-University Erlangen. |