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11-04-2025 | Computed Tomography | Review Article

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

Authors: Ahmed Msherghi, Maram Abuajamieh, Moad Ekreer, Muhab Alzlitni, Mohamed Hajalamin, Ebtesam Aldieb, Dua Rajab Khalleefah, Abdussalam I. A. Alzein, Imane Chenfouh, Hudi Mohammed, Abdulmhoimen Elkhadar, Ahmed Benghatnsh, Hamza Adel Salim, Mohamed Alsharedi, Muhammed Elhadi, Max Wintermark, Abass Alavi

Published in: European Journal of Nuclear Medicine and Molecular Imaging

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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.
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Literature
1.
go back to reference Tariq NU, McNamara MG, Valle JW. Biliary tract cancers: current knowledge, clinical candidates and future challenges. Cancer Manag Res. 2019;11:2623–42.PubMedPubMedCentralCrossRef Tariq NU, McNamara MG, Valle JW. Biliary tract cancers: current knowledge, clinical candidates and future challenges. Cancer Manag Res. 2019;11:2623–42.PubMedPubMedCentralCrossRef
5.
go back to reference Oh DY, et al. Durvalumab plus gemcitabine and cisplatin in advanced biliary tract cancer. NEJM Evid. 2022;1(8):EVIDoa2200015.PubMedCrossRef Oh DY, et al. Durvalumab plus gemcitabine and cisplatin in advanced biliary tract cancer. NEJM Evid. 2022;1(8):EVIDoa2200015.PubMedCrossRef
6.
go back to reference Kang MJ, et al. Distinct prognosis of biliary tract cancer according to tumor location, stage, and treatment: a population-based study. Sci Rep. 2022;12(1):10206.PubMedPubMedCentralCrossRef Kang MJ, et al. Distinct prognosis of biliary tract cancer according to tumor location, stage, and treatment: a population-based study. Sci Rep. 2022;12(1):10206.PubMedPubMedCentralCrossRef
7.
go back to reference Amit U, et al. Clinical outcomes and risk stratification in unresectable biliary tract cancers undergoing radiation therapy. Radiat Oncol. 2024;19(1):102.PubMedPubMedCentralCrossRef Amit U, et al. Clinical outcomes and risk stratification in unresectable biliary tract cancers undergoing radiation therapy. Radiat Oncol. 2024;19(1):102.PubMedPubMedCentralCrossRef
8.
go back to reference Jun SY, et al. Clinicopathologic and prognostic significance of gallbladder and cystic duct invasion in distal bile duct carcinoma. Arch Pathol Lab Med. 2020;144(6):755–63.PubMedCrossRef Jun SY, et al. Clinicopathologic and prognostic significance of gallbladder and cystic duct invasion in distal bile duct carcinoma. Arch Pathol Lab Med. 2020;144(6):755–63.PubMedCrossRef
9.
go back to reference Albazaz R, et al. Clinical impact of FDG PET-CT on management decisions for patients with primary biliary tumours. Insights Imaging. 2013;4(5):691–700.PubMedPubMedCentralCrossRef Albazaz R, et al. Clinical impact of FDG PET-CT on management decisions for patients with primary biliary tumours. Insights Imaging. 2013;4(5):691–700.PubMedPubMedCentralCrossRef
10.
go back to reference Jiang L, et al. Role of 18F-FDG PET/CT imaging in intrahepatic cholangiocarcinoma. Clin Nucl Med. 2016;41(1):1–7.PubMedCrossRef Jiang L, et al. Role of 18F-FDG PET/CT imaging in intrahepatic cholangiocarcinoma. Clin Nucl Med. 2016;41(1):1–7.PubMedCrossRef
11.
go back to reference Kim JY, et al. Clinical role of 18F-FDG PET-CT in suspected and potentially operable cholangiocarcinoma: a prospective study compared with conventional imaging. Am J Gastroenterol. 2008;103(5):1145–51.PubMedCrossRef Kim JY, et al. Clinical role of 18F-FDG PET-CT in suspected and potentially operable cholangiocarcinoma: a prospective study compared with conventional imaging. Am J Gastroenterol. 2008;103(5):1145–51.PubMedCrossRef
12.
go back to reference Lee Y, et al. The role of F-18 FDG PET/CT in intrahepatic cholangiocarcinoma. Nucl Med Mol Imaging. 2017;51(1):69–78.PubMedCrossRef Lee Y, et al. The role of F-18 FDG PET/CT in intrahepatic cholangiocarcinoma. Nucl Med Mol Imaging. 2017;51(1):69–78.PubMedCrossRef
13.
go back to reference Reinhardt MJ, et al. Detection of Klatskin’s tumor in extrahepatic bile duct strictures using delayed 18F-FDG PET/CT: preliminary results for 22 patient studies. J Nucl Med. 2005;46(7):1158–63.PubMed Reinhardt MJ, et al. Detection of Klatskin’s tumor in extrahepatic bile duct strictures using delayed 18F-FDG PET/CT: preliminary results for 22 patient studies. J Nucl Med. 2005;46(7):1158–63.PubMed
14.
go back to reference McInnes MDF, et al. Preferred reporting items for a systematic review and meta-analysis of diagnostic test accuracy studies: the PRISMA-DTA statement. JAMA. 2018;319(4):388–96.PubMedCrossRef McInnes MDF, et al. Preferred reporting items for a systematic review and meta-analysis of diagnostic test accuracy studies: the PRISMA-DTA statement. JAMA. 2018;319(4):388–96.PubMedCrossRef
16.
go back to reference Yang B, et al. QUADAS-C: a tool for assessing risk of bias in comparative diagnostic accuracy studies. Ann Intern Med. 2021;174(11):1592–9.PubMedCrossRef Yang B, et al. QUADAS-C: a tool for assessing risk of bias in comparative diagnostic accuracy studies. Ann Intern Med. 2021;174(11):1592–9.PubMedCrossRef
17.
go back to reference Whiting PF, et al. QUADAS-2: a revised tool for the quality assessment of diagnostic accuracy studies. Ann Intern Med. 2011;155(8):529–36.PubMedCrossRef Whiting PF, et al. QUADAS-2: a revised tool for the quality assessment of diagnostic accuracy studies. Ann Intern Med. 2011;155(8):529–36.PubMedCrossRef
18.
go back to reference McGuinness LA, Higgins JPT. Risk-of-bias VISualization (robvis): an R package and Shiny web app for visualizing risk-of-bias assessments. Res Synth Methods. 2021;12(1):55–61.PubMedCrossRef McGuinness LA, Higgins JPT. Risk-of-bias VISualization (robvis): an R package and Shiny web app for visualizing risk-of-bias assessments. Res Synth Methods. 2021;12(1):55–61.PubMedCrossRef
19.
go back to reference Siripongsatian D, et al. Comparisons of quantitative parameters of Ga-68-labelled fibroblast activating protein inhibitor (FAPI) PET/CT and [(18)F]F-FDG PET/CT in patients with liver malignancies. Mol Imaging Biol. 2022;24(5):818–29.PubMedPubMedCentralCrossRef Siripongsatian D, et al. Comparisons of quantitative parameters of Ga-68-labelled fibroblast activating protein inhibitor (FAPI) PET/CT and [(18)F]F-FDG PET/CT in patients with liver malignancies. Mol Imaging Biol. 2022;24(5):818–29.PubMedPubMedCentralCrossRef
20.
go back to reference Jinghua L, et al. Clinical prospective study of Gallium 68 ((68)Ga)-labeled fibroblast-activation protein inhibitor PET/CT in the diagnosis of biliary tract carcinoma. Eur J Nucl Med Mol Imaging. 2023;50(7):2152–66.PubMedCrossRef Jinghua L, et al. Clinical prospective study of Gallium 68 ((68)Ga)-labeled fibroblast-activation protein inhibitor PET/CT in the diagnosis of biliary tract carcinoma. Eur J Nucl Med Mol Imaging. 2023;50(7):2152–66.PubMedCrossRef
21.
go back to reference Pabst KM, et al. Superior tumor detection for (68)Ga-FAPI-46 versus (18)F-FDG PET/CT and conventional CT in patients with cholangiocarcinoma. J Nucl Med. 2023;64(7):1049–55.PubMedPubMedCentralCrossRef Pabst KM, et al. Superior tumor detection for (68)Ga-FAPI-46 versus (18)F-FDG PET/CT and conventional CT in patients with cholangiocarcinoma. J Nucl Med. 2023;64(7):1049–55.PubMedPubMedCentralCrossRef
22.
go back to reference Shi X, et al. Fibroblast imaging of hepatic carcinoma with (68)Ga-FAPI-04 PET/CT: a pilot study in patients with suspected hepatic nodules. Eur J Nucl Med Mol Imaging. 2021;48(1):196–203.PubMedCrossRef Shi X, et al. Fibroblast imaging of hepatic carcinoma with (68)Ga-FAPI-04 PET/CT: a pilot study in patients with suspected hepatic nodules. Eur J Nucl Med Mol Imaging. 2021;48(1):196–203.PubMedCrossRef
23.
go back to reference Rajaraman V, et al. Role of 68Ga-FAPI PET/CT in assessing hepatobiliary malignancies: a prospective pilot study. Clin Nucl Med. 2023;48(6):e281–8.PubMedCrossRef Rajaraman V, et al. Role of 68Ga-FAPI PET/CT in assessing hepatobiliary malignancies: a prospective pilot study. Clin Nucl Med. 2023;48(6):e281–8.PubMedCrossRef
24.
go back to reference Zhang Z, et al. 68 Ga-FAPI-04 PET/CT for the evaluation of cholangiocarcinoma: comparison with 18 F-FDG PET/CT and abdominal 68 Ga-FAPI-04 PET/MR. Clin Nucl Med. 2024;49(5):409–18.PubMedCrossRef Zhang Z, et al. 68 Ga-FAPI-04 PET/CT for the evaluation of cholangiocarcinoma: comparison with 18 F-FDG PET/CT and abdominal 68 Ga-FAPI-04 PET/MR. Clin Nucl Med. 2024;49(5):409–18.PubMedCrossRef
25.
go back to reference Lan L, et al. Prospective comparison of (68)Ga-FAPI versus (18)F-FDG PET/CT for tumor staging in biliary tract cancers. Radiology. 2022;304(3):648–57.PubMedCrossRef Lan L, et al. Prospective comparison of (68)Ga-FAPI versus (18)F-FDG PET/CT for tumor staging in biliary tract cancers. Radiology. 2022;304(3):648–57.PubMedCrossRef
27.
go back to reference Lamarca A, et al. Current standards and future perspectives in adjuvant treatment for biliary tract cancers. Cancer Treat Rev. 2020;84:101936.PubMedCrossRef Lamarca A, et al. Current standards and future perspectives in adjuvant treatment for biliary tract cancers. Cancer Treat Rev. 2020;84:101936.PubMedCrossRef
28.
go back to reference Delgado Bolton RC, et al. Are we approaching a change in paradigm in PET/CT imaging of solid gastrointestinal (or digestive) tract tumors with the clinical application of FAPI imaging? Clin Nucl Med. 2023;48(4):318–9.PubMedCrossRef Delgado Bolton RC, et al. Are we approaching a change in paradigm in PET/CT imaging of solid gastrointestinal (or digestive) tract tumors with the clinical application of FAPI imaging? Clin Nucl Med. 2023;48(4):318–9.PubMedCrossRef
29.
go back to reference Giesel FL, et al. FAPI-74 PET/CT Using Either (18)F-AlF or cold-kit (68)Ga labeling: biodistribution, radiation dosimetry, and tumor delineation in lung cancer patients. J Nucl Med. 2021;62(2):201–7.PubMedPubMedCentralCrossRef Giesel FL, et al. FAPI-74 PET/CT Using Either (18)F-AlF or cold-kit (68)Ga labeling: biodistribution, radiation dosimetry, and tumor delineation in lung cancer patients. J Nucl Med. 2021;62(2):201–7.PubMedPubMedCentralCrossRef
30.
go back to reference Dong Y, Zhou H, Alhaskawi A, Wang Z, Lai J, Yao C, Liu Z, Hasan Abdullah Ezzi S, Goutham Kota V, Hasan Abdulla Hasan Abdulla M, Lu H. The superiority of fibroblast activation protein inhibitor (FAPI) PET/CT versus FDG PET/CT in the diagnosis of various malignancies. Cancers (Basel). 2023;15(4):1193. https://doi.org/10.3390/cancers15041193 Dong Y, Zhou H, Alhaskawi A, Wang Z, Lai J, Yao C, Liu Z, Hasan Abdullah Ezzi S, Goutham Kota V, Hasan Abdulla Hasan Abdulla M, Lu H. The superiority of fibroblast activation protein inhibitor (FAPI) PET/CT versus FDG PET/CT in the diagnosis of various malignancies. Cancers (Basel). 2023;15(4):1193. https://​doi.​org/​10.​3390/​cancers15041193
31.
go back to reference Gege Z, Xueju W, Bin J. Head-To-head comparison of (68)Ga-FAPI PET/CT and FDG PET/CT for the detection of peritoneal metastases: systematic review and meta-analysis. AJR Am J Roentgenol. 2023;220(4):490–8.PubMedCrossRef Gege Z, Xueju W, Bin J. Head-To-head comparison of (68)Ga-FAPI PET/CT and FDG PET/CT for the detection of peritoneal metastases: systematic review and meta-analysis. AJR Am J Roentgenol. 2023;220(4):490–8.PubMedCrossRef
32.
go back to reference Gao C, et al. Head to head comparison of (68)Ga-FAPI PET/CT with (18)F-FDG PET/CT in primary and metastatic lesions of gastric tumor: a systematic review and meta-analysis. Hell J Nucl Med. 2024;27(1):35–45.PubMed Gao C, et al. Head to head comparison of (68)Ga-FAPI PET/CT with (18)F-FDG PET/CT in primary and metastatic lesions of gastric tumor: a systematic review and meta-analysis. Hell J Nucl Med. 2024;27(1):35–45.PubMed
33.
go back to reference Hirmas N, et al. Diagnostic accuracy 68Ga-FAPI versus 18F-FDG PET in patients with various malignancies. J Nucl Med. 2024;65(3):372–8.PubMedCrossRef Hirmas N, et al. Diagnostic accuracy 68Ga-FAPI versus 18F-FDG PET in patients with various malignancies. J Nucl Med. 2024;65(3):372–8.PubMedCrossRef
35.
go back to reference Lindner T, et al. Development of quinoline-based theranostic ligands for the targeting of fibroblast activation protein. J Nucl Med. 2018;59(9):1415–22.PubMedCrossRef Lindner T, et al. Development of quinoline-based theranostic ligands for the targeting of fibroblast activation protein. J Nucl Med. 2018;59(9):1415–22.PubMedCrossRef
36.
go back to reference Guo W, et al. Imaging fibroblast activation protein in liver cancer: a single-center post hoc retrospective analysis to compare [68Ga]Ga-FAPI-04 PET/CT versus MRI and [18F]-FDG PET/CT. Eur J Nucl Med Mol Imaging. 2021;48(5):1604–17.PubMedCrossRef Guo W, et al. Imaging fibroblast activation protein in liver cancer: a single-center post hoc retrospective analysis to compare [68Ga]Ga-FAPI-04 PET/CT versus MRI and [18F]-FDG PET/CT. Eur J Nucl Med Mol Imaging. 2021;48(5):1604–17.PubMedCrossRef
38.
go back to reference Fouillet J, et al. Unveiling the tumor microenvironment through fibroblast activation protein targeting in diagnostic nuclear medicine: a didactic review on biological rationales and key imaging agents. Biology. 2024;13(12):967.PubMedPubMedCentralCrossRef Fouillet J, et al. Unveiling the tumor microenvironment through fibroblast activation protein targeting in diagnostic nuclear medicine: a didactic review on biological rationales and key imaging agents. Biology. 2024;13(12):967.PubMedPubMedCentralCrossRef
39.
40.
go back to reference Hagiwara A, et al. Variability and standardization of quantitative imaging: monoparametric to multiparametric quantification, radiomics, and artificial intelligence. Invest Radiol. 2020;55(9):601–16.PubMedPubMedCentralCrossRef Hagiwara A, et al. Variability and standardization of quantitative imaging: monoparametric to multiparametric quantification, radiomics, and artificial intelligence. Invest Radiol. 2020;55(9):601–16.PubMedPubMedCentralCrossRef
42.
go back to reference Galgano SJ, et al. Applications of PET/MRI in abdominopelvic oncology. Radiographics. 2021;41(6):1750–65.PubMedCrossRef Galgano SJ, et al. Applications of PET/MRI in abdominopelvic oncology. Radiographics. 2021;41(6):1750–65.PubMedCrossRef
44.
go back to reference Han J, et al. 18F half-life measurement using a high-purity germanium detector. Appl Radiat Isot. 2012;70(11):2581–5.PubMedCrossRef Han J, et al. 18F half-life measurement using a high-purity germanium detector. Appl Radiat Isot. 2012;70(11):2581–5.PubMedCrossRef
45.
go back to reference Sanchez-Crespo A. Comparison of Gallium-68 and Fluorine-18 imaging characteristics in positron emission tomography. Appl Radiat Isot. 2013;76:55–62.PubMedCrossRef Sanchez-Crespo A. Comparison of Gallium-68 and Fluorine-18 imaging characteristics in positron emission tomography. Appl Radiat Isot. 2013;76:55–62.PubMedCrossRef
46.
go back to reference Hu K, et al. [(18)F]FAPI-42 PET imaging in cancer patients: optimal acquisition time, biodistribution, and comparison with [(68)Ga]Ga-FAPI-04. Eur J Nucl Med Mol Imaging. 2022;49(8):2833–43.PubMedCrossRef Hu K, et al. [(18)F]FAPI-42 PET imaging in cancer patients: optimal acquisition time, biodistribution, and comparison with [(68)Ga]Ga-FAPI-04. Eur J Nucl Med Mol Imaging. 2022;49(8):2833–43.PubMedCrossRef
47.
go back to reference Zhang J, et al. [18F]FAPI PET/CT in the evaluation of focal liver lesions with [18F]FDG non-avidity. Eur J Nucl Med Mol Imaging. 2023;50(3):937–50.PubMedCrossRef Zhang J, et al. [18F]FAPI PET/CT in the evaluation of focal liver lesions with [18F]FDG non-avidity. Eur J Nucl Med Mol Imaging. 2023;50(3):937–50.PubMedCrossRef
Metadata
Title
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
Authors
Ahmed Msherghi
Maram Abuajamieh
Moad Ekreer
Muhab Alzlitni
Mohamed Hajalamin
Ebtesam Aldieb
Dua Rajab Khalleefah
Abdussalam I. A. Alzein
Imane Chenfouh
Hudi Mohammed
Abdulmhoimen Elkhadar
Ahmed Benghatnsh
Hamza Adel Salim
Mohamed Alsharedi
Muhammed Elhadi
Max Wintermark
Abass Alavi
Publication date
11-04-2025
Publisher
Springer Berlin Heidelberg
Published in
European Journal of Nuclear Medicine and Molecular Imaging
Print ISSN: 1619-7070
Electronic ISSN: 1619-7089
DOI
https://doi.org/10.1007/s00259-025-07264-5