Clinical results of fibroblast activation protein (FAP) specific PET for non-malignant indications: systematic review

PURPOSE: Small molecules targeting fibroblast activation protein (FAP) have emerged as a new group of tracers for positron emission tomography (PET) in 2018. While most of the existing literature has been focussed on the application of FAP-specific PET in various kinds of cancers, some researchers have, both intentionally or unintentionally, used FAP-specific PET in patients with non-cancerous diseases. The purpose of this systematic review is therefore to summarize the available evidence of FAP-specific PET for non-malignant indications. METHODS: The MEDLINE database was searched for studies presenting the clinical use of FAP-specific PET, the records were screened according to PRISMA guidelines and articles containing patients suffering from non-malignant diseases were included. RESULTS: Sixteen studies with 303 patients were included. FAP-specific PET has been used in cardiac imaging, IgG(4)-related disease, benign tumors as well as various kinds of inflammation. Two prospective studies on FAP-specific PET for IgG(4)-related disease show its potential to differentiate inflammatory from fibrotic lesions, which could be used to determine the management of these patients. CONCLUSION: While publications on FAP-specific PET for non-malignant indications are mostly limited to case reports and incidental findings, the first retrospective and prospective studies present promising results for IgG(4)-related as well as cardiovascular disease that warrant further research. Several currently recruiting trials will add to the body evidence in the next few years.