The comparative diagnostic and therapeutic application value of FAPI PET/CT and ¹⁸F-FDG PET/CT in oncology

Molecular imaging has become central to oncologic diagnosis and therapy assessment. ¹⁸F-fluorodeoxyglucose positron emission tomography/computed tomography (¹⁸F-FDG PET/CT) is widely implemented, yet performance is attenuated in tumors with low glycolytic activity or in sites with high physiological uptake. Small-molecule fibroblast activation protein inhibitors (FAPI) enable high-contrast imaging of cancer-associated fibroblasts within the tumor stroma, offering rapid clearance and favorable biodistribution. This review synthesizes clinical and preclinical evidence comparing FAPI PET/CT with¹⁸F-FDG PET/CT across solid tumors. Head-to-head analyses indicate superior or complementary lesion conspicuity for FAPI in pancreatic ductal adenocarcinoma and colorectal cancer (CRC) -especially peritoneal and nodal disease-and context-dependent comparability in breast and head-and-neck cancers. Across studies, FAPI demonstrates higher tumor-to-background ratios and improved detection of small or low-FDG-avid lesions, with variable downstream effects on staging and management. We delineate disease-specific scenarios in which multi-tracer strategies may optimize diagnostic yield and propose a framework for integrating FAPI into precision imaging pathways. Priority areas include prospective, adequately powered trials; harmonized acquisition and quantification protocols; and evaluations of cost-effectiveness and theranostic implications.