The comparative utility of FAPI-based PET radiotracers over [¹⁸F]FDG in the assessment of malignancies

Fibroblast activation protein (FAP) is a type II transmembrane serine protease overexpressed in cancer-associated fibroblasts (CAFs) and has been associated with poor prognosis. PET/CT imaging with radiolabeled FAP inhibitors (FAPI) is currently being studied for various malignancies. This review identifies the uses and limitations of FAPI PET/CT in malignancies and compares the advantages and disadvantages of FAPI and ¹⁸F-fluorodeoxyglucose ([¹⁸F]FDG). Due to high uptake, rapid clearance from the circulation, and limited uptake in normal tissue, FAPI tumor-to-background contrast ratios are equivalent to or better than [¹⁸F]FDG in most applications. In several settings, FAPI has shown greater uptake specificity than [¹⁸F]FDG and improved sensitivity in detecting lymph node, bone, and visceral tissue metastases. Therefore, FAPI PET/CT may be complementary in distinguishing pathological lesions with conventional imaging, determining the primary site of malignancy, improving tumor staging, and detecting disease recurrence, especially in patients with inconclusive [¹⁸F]FDG PET/CT findings. Nevertheless, FAPI has limitations, including certain settings with non-specific uptake, modified uptake with age and menopause status, challenges with clinical access, and limited clinical evidence.