⁶⁸Ga-FAPI-04 PET/CT for molecular assessment of fibroblast activation and risk evaluation in systemic sclerosis-related interstitial lung disease

Ziel/Aim Interstitial lung disease (ILD) is the most common cause of death in systemic sclerosis (SSc). To date, the progression of SSc-ILD is judged by the accrual of lung damage on computed tomography (CT) and lung function testing. However, diagnostic tools to assess current activity are lacking. Here, we tested the hypothesis that quantification of fibroblast activation by FAPI PET/CT may correlate with ILD activity and disease progression in SSc-ILD.

Methodik/Methods 21 patients with SSc-ILD confirmed by HRCT and 21 controls without ILD were consecutively enrolled. All participants underwent FAPI PET/CT imaging and standard-of-care procedures including HRCT and lung function testing (PFT) at baseline. Patients with SSc-ILD patients were followed-up for 6 months with HRCT and PFT. We compared baseline FAPI PET/CT uptake to standard diagnostic tools and currently used predictors of ILD progression. Follow-up FAPI PET/CT scans were obtained in a subset of patients treated with nintedanib to assess change over time.

Ergebnisse/Results FAPI accumulated in fibrotic areas of the lungs in SSc-ILD compared to controls with a median wlSUV_mean of 0.8 (0.6 to 2.1) in the SSc-ILD group and 0.5 (0.4 to 0.5) in the control group (p < 0.0001) and a median whole lung maximal standardized uptake value (wlSUV_max) of 4.4 (3.05 to 5.2) in the SSc-ILD group compared to 0.7 (0.65 to 0.7) in the control group (p < 0.0001). FAPI uptake was higher in patients with extensive disease, with previous ILD progression or high EUSTAR activity scores. Increased FAPI uptake at baseline was associated with progression of ILD independently of extent of involvement on HRCT scan and the forced vital capacity at baseline. In consecutive FAPI PET/CTs, changes in tracer uptake was concordant with the observed response to the fibroblast-targeting antifibrotic agent nintedanib.

Schlussfolgerungen/Conclusions 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 FAPI PET/CT may be of potential to improve risk assessment of SSc-ILD.

Publication History

Article published online:
08 April 2021