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April 16, 2026Respiratory Research0 citationsOpen Access

Fibroblast activation protein inhibitor (FAPI) PET imaging in pulmonary fibrosis: pathophysiology, clinical utility, and emerging theranostic applications

AAAli Al-waqeerahHHHuanyu HeABAhmed Bashah

Key Result

FAPI PET imaging detects early fibroblast activation and fibrotic activity prior to structural changes visible on conventional CT in preclinical models of pulmonary fibrosis.

Key Points

  • The aim is to explore FAPI PET imaging as a means to visualize active fibrogenesis in pulmonary fibrosis and assess its clinical utility.
  • Review of FAP biology and FAPI radiotracer development
  • Analysis of preclinical and early human studies
  • Assessment of FAPI-PET/CT in interstitial lung diseases
  • Discussion on FAP-expressing fibroblast subsets and challenges in interpretation
  • FAPI-PET imaging shows promise in detecting early fibroblast activation
  • Evidence indicates potential for risk stratification in pulmonary fibrosis
  • FAPI imaging could aid in monitoring therapy responses
  • Current evidence supporting clinical utility is limited and requires further prospective studies

Structured PICO

Does FAPI-PET/CT imaging improve the detection of early fibroblast activation, risk stratification, and therapy monitoring in patients with pulmonary fibrosis?

P
Population
Patients with interstitial lung diseases/pulmonary fibrosis and preclinical models
I
Intervention
Fibroblast activation protein inhibitor (FAPI)-based radiotracers for positron emission tomography (PET/CT)

FAPI-PET/CT is an emerging molecular imaging modality that shows promise for early detection of active fibrogenesis and risk stratification in pulmonary fibrosis, potentially overcoming the limitations of conventional HRCT.

Limitations

  • Current evidence remains limited and preliminary
  • Human data is largely derived from small pilot cohorts rather than large controlled studies
  • Interpretive challenges exist due to the functional heterogeneity of FAP-expressing fibroblast subsets
  • Lack of direct comparisons between different FAPI tracers in interstitial lung disease
  • Current evidence remains limited
  • Interpretive challenges due to functional heterogeneity of FAP-expressing fibroblast subsets
  • Prospective studies are needed to clarify clinical utility

Abstract

Pulmonary fibrosis arises from a dysregulated wound-healing response in which activated fibroblasts drive excessive extracellular matrix deposition and irreversible lung architectural distortion. Conventional high-resolution computed tomography (HRCT) detects largely established structural damage, limiting opportunities for early intervention. The fibroblast activation protein (FAP), a membrane-bound serine protease expressed on activated fibroblasts, presents a potential molecular target for imaging active fibrogenesis. The advent of fibroblast activation protein inhibitor (FAPI)–based radiotracers for positron emission tomography (PET) has been developed to visualize FAP expression in vivo. This review traces the translational continuum from FAP biology through radiotracer development to clinical application of FAPI-PET/CT in interstitial lung diseases, summarising preclinical and emerging human studies investigating FAPI PET/CT in interstitial lung diseases, highlighting preliminary evidence for the detection of early fibroblast activation, potential risk stratification, and monitoring of therapy response. We also discuss the functional heterogeneity of FAP-expressing fibroblast subsets and the interpretive challenges this poses for FAPI imaging. The review also considers early translational work on FAPI-based theranostics, combining diagnostic imaging with fibroblast-targeted radioligand approaches. While FAPI-PET/CT shows promise as a tool for characterizing fibrogenic activity, current evidence remains limited, and prospective studies are needed to clarify its clinical utility and potential role in guiding personalized interventions.

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Cite This Study

Al-waqeerah et al. (2026) conducted a review in Pulmonary fibrosis. Fibroblast activation protein inhibitor (FAPI) PET imaging was evaluated. FAPI PET imaging detects early fibroblast activation and fibrotic activity prior to structural changes visible on conventional CT in preclinical models of pulmonary fibrosis.

synapsesocial.com/papers/69e07d732f7e8953b7cbe622https://doi.org/10.1186/s12931-026-03661-y
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Also Consider

Synapse has enriched 5 closely related papers on similar clinical questions. Consider them for comparative context:

  1. 1Enhanced Detection of Early Pulmonary Fibrosis Disease Using 68Ga-FAPI-LM3 PET2024 · 10 citations
  2. 2The Role of Cytokines and Molecular Pathways in Lung Fibrosis Following SARS-CoV-2 Infection: A Physiopathologic (Re)view2024 · 31 citations
  3. 3FAP expression in alpha cells of Langherhans insulae—implications for FAPI radiopharmaceuticals’ use2023 · 9 citations
  4. 4Fibrocytes in the Pathogenesis of Chronic Fibrotic Lung Disease2013 · 9 citations
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