Abstract
Systemic sclerosis-associated interstitial lung disease (SSc-ILD) is a leading cause of morbidity and mortality in patients with systemic sclerosis. High-resolution computed tomography (HRCT) provides anatomical detail but cannot directly assess disease activity, inflammation, or fibroblast activation. Molecular positron emission tomography/computed tomography (PET/CT) offers functional imaging that may complement structural assessment. This narrative review examines the role of molecular PET/CT in SSc-ILD, including fluorodeoxyglucose (FDG) PET/CT for metabolic activity assessment, fibroblast activation protein inhibitor (FAPI) tracers for fibrosis imaging, and other molecular probes targeting inflammation and tissue remodelling. We synthesize evidence on the diagnostic feasibility, prognostic value, and clinical applications of molecular PET/CT in SSc-ILD and related fibrotic interstitial lung diseases. Quantitative PET metrics, radiomics approaches, and artificial intelligence integration are also discussed. Although molecular PET/CT shows potential for phenotyping disease activity and predicting outcomes, current evidence is limited by small sample sizes and heterogeneous study designs. Standardization of imaging protocols, validation in multicenter cohorts, and integration with clinical and molecular biomarkers are needed before the clinical utility of molecular PET/CT in SSc-ILD can be established.