Head-to-head Comparison of [68Ga]Ga-FAPI-04 PET and [18F]FDG PET in the Evaluation of Primary Gastrointestinal Tumors and Metastases: A Systematic Review and Meta-analysis.

Objective: Gastrointestinal cancers pose a major public health challenge due to very aggressive malignancy, the quick and widespread metastases, relapse frequently in lymph node and omentum, and poor prognosis. [68Ga]Ga-FAPI-04 PET is widely used to diagnose gastrointestinal tumors. This study aimed to conduct a head-to-head comparison of the [68Ga]Ga-FAPI-04 and [18F]-FDG imaging methods for diagnosing primary gastrointestinal tumors and metastases.

Methods: The PubMed, Embase, Web of Science, and Cochrane Library databases were systematically searched up to 16 April 2024. The included studies involved head-to-head comparisons to evaluate [68Ga]Ga-FAPI-04 and [18F]FDG PET in gastrointestinal cancers. QUADAS-2 was used to assess the quality of the included articles.

Results: The study included 16 studies. Nine studies were performed on gastric cancer, four on colorectal cancer, and the remaining three studies of various gastrointestinal tumors, including gastric, duodenal, appendiceal and colorectal cancers. The total number of patients was 597, including 384 males. In gastric cancer, [68Ga]Ga-FAPI-04 PET demonstrated superior sensitivity for the primary tumors (0.98 vs. 0.74) and lymph node metastases (0.90 vs. 0.45) than [18F]FDG. In gastric cancer, [68Ga]Ga-FAPI-04 PET demonstrated superior specificity for the primary tumors (0.93 vs. 0.48) and lymph node metastases (0.93 vs. 0.83) than [18F]FDG. [68Ga]Ga-FAPI-04 PET had a sensitivity of 0.99 (95% CI 0.19-1.00) for gastric signet-ring-cell carcinoma (GSRCC), and [18F]FDG PET had a sensitivity of 0.46 for GSRCC. There was a significant difference in mean difference (MD) of SUVmax (MD 5.75 [95% CI 1.42-10.08]) for GSRCC between [68Ga]Ga-FAPI-04 and [18F]FDG. In colorectal cancer, [68Ga]Ga-FAPI-04 PET was more sensitive for primary tumors (1.00 vs. 0.97). In gastrointestinal cancers, [68Ga]Ga-FAPI-04 PET showed superior pooled sensitivity compared with [18F]FDG for primary tumors (0.99 [95% CI 0.95-1.00] vs. 0.82 [95% CI 0.67-0.91]), metastatic lymph nodes (0.95 [95% CI 0.81-0.99] vs. 0.56 [95% CI 0.43-0.69]), distant metastases (0.93 vs. 0.63), and peritoneal metastases (0.99 vs. 0.51). In gastrointestinal cancers, [68Ga]Ga-FAPI-04 PET showed superior pooled specificity compared with [18F]FDG for primary tumors (0.90 vs. 0.74), and metastatic lymph nodes (0.89 vs. 0.84). Furthermore, [68Ga]Ga-FAPI-04 had a superior SUVmax and TBR compared with [18F]FDG for primary gastrointestinal tumors and metastases.

Conclusions: [68Ga]Ga-FAPI-04 PET demonstrated superior sensitivity and specificity in primary gastrointestinal cancers and metastases in comparison with [18F]FDG. The results demonstrated that [68Ga]Ga-FAPI-04 PET was a more suitable modality than [18F]FDG PET for the diagnosis of SRCC.