18F-Fibroblast Activation Protein Inhibitor Positron Emission Tomography Imaging as a Biomarker of Fibrosis and Tissue Remodeling: Implications for Regenerative Medicine

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BSTRACT

Fibrosis (FIB) and tissue remodeling are central processes in a wide range of pathological and regenerative conditions. Fibroblast activation protein (FAP), selectively expressed in activated fibroblasts, has emerged as a promising molecular target for non-invasive imaging. Radiolabeled FAP inhibitors (FAPIs), particularly ¹⁸ F-FAPI, enable visualization of fibroblast activity in vivo using positron emission tomography (PET). This narrative review summarizes current evidence on FAPI-based PET imaging as a biomarker of FIB and tissue remodeling, with a focus on its implications for regenerative medicine. A systematic literature search identified 14 relevant studies, primarily clinical investigations evaluating FAPI PET across multiple organ systems, including liver, lung, heart, kidney, and systemic fibrotic diseases. The included studies consistently demonstrate that FAPI uptake correlates with fibroblast activation, extracellular matrix remodeling, and disease severity. Clinical applications include staging of liver FIB, prediction of cardiac remodeling outcomes, assessment of interstitial lung disease progression, and multiorgan FIB mapping in systemic sclerosis. Importantly, FAPI PET shows superior specificity for fibrotic activity compared to conventional imaging modalities such as ¹⁸ F-fluorodeoxyglucose. These findings highlight the potential of ¹⁸ F-FAPI PET as a noninvasive biomarker bridging molecular imaging and regenerative medicine. Future research should focus on longitudinal validation, integration with regenerative therapies, and development of theranostic applications.