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Review
. 2025 Sep;52(11):4200-4212.
doi: 10.1007/s00259-025-07264-5. Epub 2025 Apr 11.

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

Ahmed Msherghi  1 , Maram Abuajamieh  2 , Moad Ekreer  3 , Muhab Alzlitni  4 , Mohamed Hajalamin  5 , Ebtesam Aldieb  6 , Dua Rajab Khalleefah  7 , Abdussalam I A Alzein  8 , Imane Chenfouh  9 , Hudi Mohammed  10 , Abdulmhoimen Elkhadar  4 , Ahmed Benghatnsh  11 , Hamza Adel Salim  1 , Mohamed Alsharedi  12 , Muhammed Elhadi  13 , Max Wintermark  1 , Abass Alavi  14
Affiliations
Review

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

Ahmed Msherghi et al. Eur J Nucl Med Mol Imaging. 2025 Sep.

Abstract

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.

Keywords: Biliary tract cancers; Cholangiocarcinoma; [18 F]FDG; [68 Ga]Ga-FAPI.

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Conflict of interest statement

Declarations. Ethics approval: Not applicable. This study is a systematic review and meta-analysis and did not involve direct research on human or animal subjects. Consent to participate: Not applicable. This study did not involve the direct participation of individuals. Consent for publication: Not applicable. The manuscript does not include individual data requiring consent for publication. Conflict of interest: The authors declare no conflicts of interest relevant to this study. Declaration of generative AI in scientific writing: During the preparation of this work, the authors used ChatGPT- 4 solely for grammar and language improvement purposes. No assistance from this tool was employed in methodology or analysis. After using this tool, the authors reviewed and edited the content as needed and took full responsibility for the content of the published article.

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