Fibroblast Activation Protein Inhibitor (FAPI) PET: A Scoping Review of Emerging Oncologic and Fibroinflammatory Applications.

Authors

Emmanouil Panagiotidis, Filippos Koinis, Jules Zhang-Yin, George Angelidis, Varvara Valotassiou, Ioannis Tsougos, Athanasios Kotsakis, Panagiotis Georgoulias

Published in

Diagnostics (Basel, Switzerland). Volume 16. Issue 10. May 19, 2026. Epub May 19, 2026.

Abstract

This scoping review was conducted in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses Extension for Scoping Reviews (PRISMA-ScR) guidelines. It summarizes advances in fibroblast activation protein inhibitor (FAPI) positron emission tomography (PET) for oncologic and fibroinflammatory diseases. FAP is expressed broadly on activated mesenchymal cells-including cancer-associated fibroblasts (CAFs) and myofibroblasts within desmoplastic tumor stroma, FAP-positive tumor cells in selected sarcomas, and activated fibroblasts in chronic fibroinflammatory disorders such as rheumatoid arthritis, Crohn's disease, and organ fibrosis. By targeting these activated fibroblasts, [⁶⁸Ga]- and [¹⁸F]-labeled FAPI tracers provide high tumor-to-background contrast, particularly in desmoplastic and stromal-rich cancers. Compared with [¹⁸F]FDG, FAPI PET demonstrates superior lesion conspicuity in selected malignancies and enables a streamlined, non-fasting imaging workflow. Beyond oncology, FAPI PET is emerging as a promising tool for assessing cardiac fibrosis, pulmonary inflammation, and autoimmune conditions characterized by fibroblast activation. A systematic literature search of PubMed and Scopus was performed for peer-reviewed publications from 1 January 2018 to 28 February 2026. Inclusion criteria encompassed original studies, systematic reviews, meta-analyses, clinical guidelines, case series, and case reports reporting on FAPI-targeted PET in human subjects or translational models, published in English. After screening, 256 sources met the eligibility criteria and are included. The development of standardized SNMMI/EANM imaging protocols, along with ongoing multicenter trials and the first prospective phase 2 clinical trial of ⁶⁸Ga-FAPI-46 PET with histopathological confirmation, now supports the reproducible implementation of FAPI PET across institutions. FAPI PET demonstrates strong translational potential, largely due to its favorable biodistribution, safety profile, and theranostic flexibility. However, its widespread use in routine clinical practice is contingent upon large-scale clinical validation, structured reader training, and formal regulatory approval. In conclusion, FAPI PET represents a maturing molecular imaging platform targeting activated fibroblasts across oncologic and fibroinflammatory diseases. Its widespread adoption into clinical practice requires large-scale prospective trials, reader training, standardized reporting, and regulatory approval-all of which are now actively underway.

PMID:
42196913
Bibliographic data and abstract were imported from PubMed on 14 Sep 2026.

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