Head to head comparison of 68GaGa-FAPI-04 and 18FFDG PET/CT in the diagnosis and staging of pancreatic cancer: a prospective study

68 GaGa-FAPI-04 targets FAP overexpressed in pancreatic cancer microenvironment. This study compared diagnostic efficacy and clinical impact with 18 FFDG PET/CT in pancreatic cancer. Of 97 suspected pancreatic cancer patients (58 males; mean age 63.0 ± 10.1 years), 88 were confirmed as pancreatic cancer (57 by pathology, 31 by imaging follow‑up). 68 GaGa-FAPI-04 PET/CT showed significantly higher SUVmax than 18 FFDG PET/CT in primary lesions (10.2 ± 3.5, 95%CI: 9.320-11.126 vs. 6.1 ± 3.8, 95%CI: 5.092–7.152; p = 0.001) and lymph node metastases (4.1 ± 2.4, 95%CI: 3.718–4.559 vs. 3.3 ± 2.3, 95%CI: 2.845–3.714; p = 0.001), with superior AUCs for primary tumors and lymph nodes(0.851, 95% CI: 0.735–0.981 vs. 0.802, 95% CI: 0.354–0.803; p = 0.001) (0.867, 95% CI: 0.827–0.907 vs. 0.701, 95% CI: 0.641–0.761; p = 0.001). The T/B ratio of bone and visceral metastases was higher in 68 GaGa-FAPI-04 PET/CT than 18 FFDG PET/CT(4.7 ± 3.1, 95%CI: 4.108–5.245 vs. 2.5 ± 1.6, 95%CI: 2.231–2.835; p = 0.001) with superior AUC(0.938, 95% CI: 0.912–0.964 vs. 0.919, 95% CI: 0.886–0.951; p = 0.040), as were liver (5.0 ± 4.0, 95%CI: 3.706–6.284 vs. 2.7 ± 1.3, 95%CI: 2.211–3.131; p = 0.001), peritoneal (5.4 ± 3.3, 95%CI: 4.318–6.482 vs. 3.0 ± 2.1. 95%CI: 2.211–3.745; p = 0.001) and other organ metastases (4.4 ± 2.5, 95%CI: 3.756–5.035 vs. 2.7 ± 1.7, 95%CI: 1.379–2.254; p = 0.001). 68 GaGa‑FAPI‑04 SUVmax and TBR were positive predictors for primary tumors (SUVmax: OR = 1.951, 95%CI: 1.286–2.960, p = 0.004) and nodal metastases (SUVmax: OR = 4.199, 95%CI: 2.970–5.939, p = 0.001; TBR: OR = 14.502, 95%CI: 7.228–29.095, p = 0.001). For bone and visceral metastases, both tracers were positive predictors, but 68 GaGa‑FAPI‑04 SUVmax (OR = 2.925, 95%CI: 2.048–4.177, p = 0.003) and T/B ratio (OR = 3.520, 95%CI: 2.311–5.362, p = 0.001) outperformed 18 FFDG (SUVmax: OR = 1.901, 95%CI: 1.308–2.761, p = 0.003; T/B ratio: OR = 2.480, 95%CI: 1.488–4.136, p = 0.001). Furthermore, 68 GaGa-FAPI-04 achieved higher accuracy (93.2% vs. 72.7%, p = 0.007), revised the staging of 7 patients and altered the treatment (surgical resection to unresectable) in 6 patients. Limitations include single‑center, short follow‑up, small subgroups (e.g., recurrent lesions) and incomplete pathologically confirmation. 68 GaGa-FAPI-04 PET/CT suggested potentially better diagnostic performance to 18 FFDG PET/CT and improves staging and clinical decision-making in pancreatic cancer, suggesting potential clinical value.