Nonmalignant findings on FAPI PET: An updated rapid systematic review of the literature

Fibroblast activation protein inhibitor (FAPI) PET has shown promising diagnostic performance across various cancers. However, uptake in nonmalignant conditions has also been reported, as highlighted in the authors' previous systematic review from 2022. This updated systematic review summarizes the accumulated evidence on nonmalignant FAPI PET findings, both pitfalls in cancer diagnostic and emerging novel FAPI PET scan indications.

A systematic search of PubMed, Embase, and Web of Science was conducted on May 2, 2025. Peer-reviewed English-language studies involving human subjects and using FAPI tracers, specifically targeting FAP, were included. Studies published between April 2022 and May 2025 reporting nonmalignant FAPI PET/CT findings were added to those from the previous 2022 review. Findings were analyzed on a per-lesion basis and grouped by anatomical region.

In total, 380 studies reporting 8,230 nonmalignant FAPI PET findings were included. Most studies originated from China (70%), and 63% were case reports or case series. Although 69% of subjects were scanned due to "cancer", a clear increase in nonmalignant scan indications was observed. The search identified common pitfalls for cancer diagnostics, including FAPI uptake in infectious and inflammatory diseases, fibrosis, and benign neoplasms, but also emerging nonmalignant FAPI PET indications, including interstitial lung disease, cardiac conditions, and arthritis.

This review provides, to the best of our knowledge, the most comprehensive summary of nonmalignant FAPI PET findings to date. It may serve as a valuable reference for researchers and clinicians interpreting FAPI PET.