Fibroblast activation protein as a biomarker of fibrotic lung disease

Idiopathic pulmonary fibrosis (IPF) is a severe, progressive, and often lethal disease. Current antifibrotic treatments only slow disease progression, and clinicians often need to wait one to two years to evaluate the treatment response. To address this, Dr Anne-Leen Deleu, nuclear medicine specialist at the institut Jules Bordet, and Prof Dr Benjamin Bondue, pulmonologist at the H.U.B. Hôpital Erasme, initiated a prospective, multi-cohort study exploring whether FAPI PET-CT can serve as an early biomarker of disease activity and prognosis.

The study includes 40 IPF patients starting antifibrotic therapy, 10 with acute exacerbations, 10 with non-IPF interstitial lung disease (ILD) beginning treatment, and 10 ILD patients listed for lung transplantation. All patients underwent FAPI PET-CT imaging, which targets the fibroblast activation protein (FAP), a marker of activated fibroblasts. Interestingly, a significantly higher FAPI uptake was observed in patients with exacerbations compared to baseline IPF patients. Furthermore, the uptake also correlated with lung function tests and with changes observed at three-month follow-up, suggesting its utility in monitoring disease activity.

Importantly, interim results also indicate that baseline FAPI uptake may predict the prognosis. In fact, higher uptake proved to be associated with progression at one-year follow-up. Thus, FAPI PET-CT may serve both as a diagnostic biomarker for disease activity and a prognostic biomarker in fibrotic ILDs, with potential future applications in differentiating fibrosis from inflammation.