Comparative diagnostic performance of [68 Ga]Ga-FAPI PET/CT and [18 F]FDGPET/CT in biliary tract cancers: a systematic review and meta-analysis

Background: Biliary tract cancers (BTCs) are aggressive malignancies with poor prognosis due to late-stage diagnosis. While [18 F]-FDG PET/CT is widely used for detection and staging, its sensitivity for certain BTC subtypes is limited, prompting the evaluation of 68 Ga-FAPI PET/CT as a promising alternative. Objective: To compare the diagnostic performance of [68 Ga]Ga-FAPI PET/CT and [18 F]FDG PET/CT in detecting BTCs, including primary tumors, lymph node involvement, and distant metastases. Methods: We searched PubMed, EMBASE, Web of Science, Scopus, and the Cochrane Library until March 2024 to identify studies that directly compared [68 Ga]Ga-FAPI and [18 F]FDG PET/CT in detecting BTCs. Sensitivity, specificity, pooled mean differences of tumor SUVmax and TBRmax, and odds ratios for detecting primary tumors, lymph nodes, and distant metastases using a random-effects model with the corresponding 95% confidence intervals were evaluated. Subgroup analyses were performed for intrahepatic cholangiocarcinoma (IHCC). Results: The pooled OR for [68 Ga]Ga-FAPI PET/CT versus [18 F]FDG PET/CT was 4.87 (95% CI: 1.75–13.56, I2 = 0.0%, p = 0.60), indicating a statistically significant preference for [68 Ga]Ga-FAPI. In the IHCC subgroup, the pooled OR was 2.98 (95% CI: 0.86–10.38, I2 = 0.0%, p = 0.63) favors [68 Ga]Ga-FAPI. Furthermore, [68 Ga]Ga-FAPI demonstrated significantly higher tumor uptake compared to [18 F]FDG PET/CT, with pooled mean differences in SUVmax of 6.47 (95% CI: 1.81–11.13) and TBRmax of 9.45 (95% CI: 3.88–15.03) across BTCs. Subgroup analysis for IHCC showed a trend favoring [68 Ga]Ga-FAPI, though the TBRmax difference did not reach statistical significance (mean difference: 7.71, 95% CI: - 0.58–16.01). For lymph node metastasis detection, [68 Ga]Ga-FAPI outperformed [18 F]FDG with an odds ratio of 2.81 (95% CI: 1.07–7.35), and for distant metastases, the odds ratio was 3.45 (95% CI: 1.12–10.63). However, moderate variability was observed across the studies for lymph nodes and organ metastases (I2 = 46.9 and 52.4%, respectively). Conclusion: [68 Ga]Ga-FAPI PET/CT offers superior diagnostic performance and tumor uptake compared to [18 F]FDG PET/CT in BTCs, particularly for lymph nodes and distant metastasis detection. These findings support the potential clinical utility of [68 Ga]Ga-FAPI PET/CT as a preferred imaging modality in BTCs, though further research is needed to standardize protocols and confirm these results in larger cohorts.