The latest developments in imaging fibroblast activation protein (FAP)

Abstract

Fibroblast activation protein (FAP), a membrane-anchored peptidase, is highly expressed in cancer-associated fibroblasts (CAFs) in more than 90% of epithelial tumors and contributes to progression and worse prognosis of different cancers. Therefore, FAP is considered a promising target for radionuclide-based approaches for diagnosis and treatment of tumors and for the diagnosis of non-malignant diseases associated with a remodeling of the extracellular matrix. Accordingly, a variety of quinolone-based FAP inhibitors (FAPI) coupled to chelators were developed displaying specific binding to human and murine FAP with a rapid and almost complete internalization. Due to a high tumor uptake and a very low accumulation in normal tissues as well as a rapid clearance from the circulation, a high-contrast is obtained for FAPI-PET/CT imaging even at 10 minutes after tracer administration. Moreover, FAPI-PET/CT provides advantages over FDG-PET/CT in several tumor entities for initial staging and detection of tumor recurrence and metastases including peritonitis carcinomatosa.