Beyond Cancer: The Role of Radiolabeled Fibroblast Activation Protein Inhibitors (FAPI) in Non-Oncological Molecular Imaging.

Radiolabeled fibroblast activation protein inhibitors (FAPIs) have emerged as promising tracers for molecular imaging, particularly in the field of oncology. However, their potential extends beyond cancer applications to a wide range of non-oncological conditions characterized by fibrosis, inflammation, and tissue remodeling. This review addresses the expanding role of FAPI-based imaging in non-malignant diseases, related to its ability to visualize and quantify fibroblast activation, a key process in various pathological conditions. We discuss the mechanism of action of FAPIs, their radiolabeling techniques, and their pharmacokinetics and biodistribution. The review then delves into the evidence supporting the use of FAPI-PET and SPECT in specific non-oncological applications, including cardiovascular diseases (myocardial infarction, atherosclerosis, cardiomyopathies, cardiac amyloidosis, and systemic vasculitis), liver fibrosis, pulmonary fibrosis (idiopathic pulmonary fibrosis and other interstitial lung diseases), renal diseases (chronic kidney disease, lupus nephritis, and IgA nephropathy), bone and joint diseases (rheumatoid arthritis, psoriatic arthritis, periprosthetic joint infection, and other bone and joint pathologies), and other inflammatory conditions (Crohn's disease and IgG4-related disease). We analyze the diagnostic performance of FAPI imaging in these conditions, comparing it with conventional imaging techniques and highlighting its advantages and limitations. Finally, we discuss the challenges and future directions in the field, including the need for standardization, validation studies, and the development of quantitative imaging biomarkers to improve the clinical utility of FAPI-based imaging in non-oncological applications. The aim of this review is to provide a comprehensive overview of the current state of FAPI imaging in non-oncological diseases, highlighting its potential to improve diagnosis, treatment planning, and monitoring of these conditions.