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Beyond Cancer: The Role of Radiolabeled Fibroblast Activation Protein Inhibitors (FAPI) in Non-Oncological Molecular
Esmail Jafari1, Malik E Juweid2, Mehrzad Bahtouee3
1The Persian Gulf Nuclear Medicine Research Center, Department of Nuclear Medicine, Molecular Imaging, and Theranostics, Bushehr Medical University Hospital, School of Medicine, Bushehr University of Medical Sciences, Bushehr, Iran (E.J., N.J., M.A.).
Abstract:
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.
Insights
Radiolabeled fibroblast activation protein inhibitors (FAPIs) offer new non-cancer imaging potential. FAPI imaging shows promise for diagnosing and monitoring various fibrotic and inflammatory diseases beyond oncology.
Area of Science:
- Nuclear Medicine
- Radiochemistry
- Molecular Imaging
Background:
- Radiolabeled fibroblast activation protein inhibitors (FAPIs) are established oncology imaging tracers.
- Fibroblast activation is central to many non-malignant fibrotic and inflammatory diseases.
- FAPI imaging's utility in non-oncological conditions is an emerging area of research.
Purpose of the Study:
- To review the expanding role of FAPI-based imaging in non-malignant diseases.
- To discuss FAPI imaging's application in various fibrotic, inflammatory, and remodeling conditions.
- To analyze diagnostic performance and future directions for FAPI imaging in non-oncological settings.
Main Methods:
- Review of existing literature on FAPI imaging in non-oncological diseases.
- Discussion of FAPI mechanism, radiolabeling, pharmacokinetics, and biodistribution.
- Analysis of FAPI-PET/SPECT evidence in cardiovascular, liver, lung, renal, and joint diseases.
Main Results:
- FAPI imaging visualizes and quantifies fibroblast activation in diverse non-malignant conditions.
- Evidence supports FAPI imaging's use in myocardial infarction, liver fibrosis, IPF, and rheumatoid arthritis.
- FAPI imaging demonstrates potential advantages over conventional techniques in specific non-oncological applications.
Conclusions:
- FAPI imaging holds significant promise for diagnosing and monitoring a broad spectrum of non-oncological diseases.
- Further standardization, validation studies, and quantitative biomarkers are needed to optimize clinical utility.
- FAPI imaging could enhance diagnosis, treatment planning, and patient monitoring in non-malignant conditions.
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