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Conventional imaging often lacks sensitivity for occult nodal and distant metastases, and FDG PET\/CT has variable performance due to low uptake in several tumour subtypes and false-positive uptake in inflammation. Fibroblast activation protein inhibitor (FAPI) PET\/CT has emerged as a promising alternative. This study compared the diagnostic accuracy of FDG PET\/CT, FAPI PET\/CT, and a dual-tracer approach in suspected HPB malignancies.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      This retrospective analysis included patients who underwent both [\n                      <jats:sup>18<\/jats:sup>\n                      F]FDG and [\n                      <jats:sup>68<\/jats:sup>\n                      Ga]Ga-FAPI-46 PET\/CT for suspected HPB cancer, including cholangiocarcinoma, gallbladder carcinoma, pancreatic carcinoma, periampullary carcinoma, and hepatocellular carcinoma. Histopathology and\/or clinical follow-up served as reference standard. FDG PET\/CT classification used an SUV\n                      <jats:sub>max<\/jats:sub>\n                      cut-off derived from receiver-operating characteristic analysis, while FAPI PET\/CT classification followed expert clinical interpretation. Sensitivity, specificity, and accuracy metrics were compared using paired statistics.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      176 patients were included. FAPI PET\/CT demonstrated higher sensitivity than FDG PET\/CT (93.0% vs. 76.5%,\n                      <jats:italic>p<\/jats:italic>\n                      \u2009=\u20090.002). Primary tumour diagnostic accuracy was 78.9% for FAPI versus 68.3% for FDG (\n                      <jats:italic>p<\/jats:italic>\n                      \u2009=\u20090.021). A dual-tracer approach did not outperform FAPI (76.7% vs. 78.9%,\n                      <jats:italic>p<\/jats:italic>\n                      \u2009=\u20090.711). For nodal disease, FAPI showed 86.8% diagnostic accuracy, compared with 71.1% for FDG (\n                      <jats:italic>p<\/jats:italic>\n                      \u2009=\u20090.004), driven by higher specificity. For distant metastases, accuracy was 83.9% for FAPI versus 80.0% for FDG (\n                      <jats:italic>p<\/jats:italic>\n                      \u2009=\u20090.625).\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>FAPI PET\/CT outperformed FDG PET\/CT in this retrospective analysis, with dual-tracer imaging offering no additional benefits. These results show great promise for clinical application of FAPI PET\/CT for the detection of HPB tumours and their metastases to be confirmed by independent prospective studies.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1007\/s00259-026-08112-w","type":"journal-article","created":{"date-parts":[[2026,8,12]],"date-time":"2026-08-12T07:10:49Z","timestamp":1786518649000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Real-world evidence in a large cohort comparing FAPI and FDG PET\/CT for hepatopancreatobiliary cancer diagnosis"],"prefix":"10.1007","author":[{"ORCID":"https:\/\/orcid.org\/0009-0001-9241-6702","authenticated-orcid":false,"given":"Suneetha","family":"Batchu","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2562-8377","authenticated-orcid":false,"given":"Mara M.K.","family":"Veenstra","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5068-8227","authenticated-orcid":false,"given":"David M.","family":"de Jong","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0163-231X","authenticated-orcid":false,"given":"Mohan Roop","family":"Jayanthi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7456-2258","authenticated-orcid":false,"given":"Erik","family":"Vegt","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7929-4464","authenticated-orcid":false,"given":"Sana F.","family":"Memon","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0743-3824","authenticated-orcid":false,"given":"Abhishek","family":"Tyagi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8979-2603","authenticated-orcid":false,"given":"Daniel","family":"Bos","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7562-8060","authenticated-orcid":false,"given":"Sundeep","family":"Lakhtakia","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9181-5499","authenticated-orcid":false,"given":"Marco J.","family":"Bruno","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7540-0496","authenticated-orcid":false,"given":"D. 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