Hao Huang

Background: Radiolabeled fibroblast activation protein inhibitors (FAPIs) have emerged as novel radiopharmaceutical agents for tumor diagnosis. Compared with [¹⁸F]fluoro-2-deoxy-D-glucose ([¹⁸F]FDG), which reflects glucose uptake in metabolically active regions, FAPIs mainly bind to the fibroblast activation protein (FAP), which is highly expressed in tumor-associated fibroblasts, forming a pronounced signal. Several studies suggested potential superiority of FAPI tracers above [¹⁸F]FDG-based imaging in a variety of tumor entities. In this systematic review, we focus on the comparison of FAPI-PET/CT and [¹⁸F]FDG-PET/CT in upper-abdominal tumors. Methods: Original research published from 1 January 2021 to 22 December 2024 was collected from the PubMed and Web of Science databases (CRD42025648267). This research included only clinical studies, excluding conference abstracts and case reports. The risk of bias was assessed with the QUADAS-2 tool, and all evaluation steps performed independently by three independent reviewers. A systematic quality assessment of the included studies was conducted based on the imaging performance of FAPI-PET/CT and [¹⁸F]FDG-PET/CT for pancreatic, liver, and gastric cancers. The meta-analysis used relative risk (RR) as the effect size, with bias assessed via the Peters test (p-value > 0.05). Cochran’s Q test and I-squared value are used to comprehensively evaluate the magnitude of heterogeneity. Analyses and data visualization were performed in R language. Results: The database search identified 3272 articles. After screening, 31 studies were included in this analysis. The original studies enrolled 1377 participants (M/F: 850/527; ages predominantly between 50 and 70). Of these, 939 patients were ultimately diagnosed with tumors (five cancer subtypes) and included in this analysis. Meta-analysis results showed that FAPI-PET/CT significantly surpassed [¹⁸F]FDG-PET/CT in the detection of primary lesions (RRs = 1.20 and 1.17), lymph nodes (RRs = 1.18 and 1.24), distant metastases (RRs = 1.22 and 1.51), peritoneal metastases (RRs = 1.31 and 2.22), and bone metastases (RRs = 1.16 and 1.23). The two imaging methods exhibit clear differences in diagnostic performance (sensitivity: 98% vs. 79%; specificity: 83% vs. 87%), and FAPI-PET/CT demonstrates high and stable diagnostic performance (RRs = 1.20 and 1.17). Conclusions: Compared with [¹⁸F]FDG-PET/CT, FAPI-PET/CT demonstrates significant advantages in detecting primary lesions, lymph nodes, distant metastases, and peritoneal and bone metastases in pancreatic, liver, and gastric cancers (RR > 1.0). Overall, FAPI-PET/CT shows better diagnostic performance (RR > 1.0).