FAPI PET/CT in infectious, inflammatory, and rheumatological diseases: “watch it like a hawk” or “one swallow does not make a summer”?

The Role of Fibroblast Activation Protein Inhibitor Positron Emission Tomography in Inflammatory and Infectious Diseases: An Updated Systematic Review

“…In this setting, fibroblast activation protein (FAP) inhibitors (FAPI), labeled with either 18 F or 68 Ga, are emerging as promising radiopharmaceuticals. FAP is a type II transmembrane serine protease belonging to the dipeptidyl peptidase 4 family, and it is highly over-expressed on the membrane of cancer-associated fibroblasts (CAFs) in about 90% of epithelial-derived cancers [3], but it may also be present in the presence of tissue damage, remodeling, or chronic inflammation, and therefore in benign conditions [4]. In contrast, healthy tissues have low expression of FAP [5].…”

“…Similar to that of 2-[ 18 F]FDG, the uptake of radiolabeled FAPI has also been described in several benign findings [10], which underlines similar specificity issues of FAPI uptake for oncological lesions. Thus, some more recently published clinical trials anticipated a function of FAPI PET for the evaluation of inflammatory and infectious diseases due to the radiolabeled FAPI uptake as a consequence of fibroblast activation in tissue remodeling, e.g., the application of FAPI PET in rheumatic diseases [4]. These recent data on the role of FAPI PET/CT in infectious and inflammatory conditions are receiving emerging attention from the scientific community.…”

Diagnostic Performance of Positron Emission Tomography with Fibroblast-Activating Protein Inhibitors in Gastric Cancer: A Systematic Review and Meta-Analysis

“…As already stated, in the tumor stroma, CAFs can express FAP, an atypical type II transmembrane serine protease, at high levels. FAP is usually undetectable in normal adult tissues, whereas its expression is significantly elevated in sites of tissue remodeling, such as inflammation and tumors [ 12 , 13 ]. According to these findings, FAP has become a potential target for the molecular imaging of many tumors, as well as non-oncological diseases, and FAP-targeting radiopharmaceuticals based on FAP-specific inhibitors (FAPi), including [ 68 Ga]Ga-FAPi-02 and [ 68 Ga]Ga-FAPi-04, have been developed [ 13 ].…”

Diagnostic Accuracy of [68Ga]Ga Labeled Fibroblast-Activation Protein Inhibitors in Detecting Head and Neck Cancer Lesions Using Positron Emission Tomography: A Systematic Review and a Meta-Analysis

“…The expression of FAP is typically low in normal adult tissues but noticeably increased in areas undergoing tissue remodeling, such as tumors and inflammation. The results indicate that FAP has emerged as a promising candidate for the molecular imaging of various tumors and non-oncological diseases [9,10]. In this regard, FAP inhibitors (FAPi) have been utilized to develop radiopharmaceuticals that can enhance the in vivo expression of FAP through PET imaging, such as [ 68 Ga]Ga-FAPi-02 and [ 68 Ga]Ga-FAPi-04 [10].…”