[18F]AlF-NOTA-FAPI-04 PET/CT outperforms contrast-enhanced CT and contrast-enhanced MRI in clinical staging evaluation of patients with initial pancreatic cancer

Contrast-enhanced CT (CE-CT) and MRI (CE-MRI) are routine examinations for staging of pancreatic cancer (PC). This study aimed to directly compare the diagnostic performance of the novel [18F]AlF-NOTA-FAPI-04 PET/CT against these established modalities for initial clinical staging. A total of 127 patients with initial PC who had simultaneously undergone [18F]AlF-NOTA-FAPI-04 PET/CT, CE-CT and CE-MRI were enrolled in this retrospective study. Their clinical features and imaging data were evaluated and staged according to TNM classification. Histopathological findings or follow-up data or multidisciplinary team (MDT) discussion served as the reference standard for the final diagnosis. For primary tumor (T) staging, CE-CT and CE-MRI demonstrated equivalent performance and outperformed [18F]AlF-NOTA-FAPI-04 PET/CT across all T stages except T1c. However, the PET/CT modality achieved significantly higher sensitivity, accuracy, and negative predictive value for both nodal (N) and distant metastasis (M) staging (all p < 0.05). It changed the N stage in 26 patients, altering management in 5 (3.93%), and revised the M stage in 16 and 18 patients compared to CE-CT and CE-MRI, respectively, leading to major treatment changes in 15 (11.81%) and 17 (13.38%) patients. A SUVmax cutoff of 4.85 for lymph node metastasis provided moderate sensitivity (67.1%) and high specificity (93.7%). [18F]AlF-NOTA-FAPI−04 PET/CT outperforms CE-CT and CE-MRI in evaluating N and M staging except T staging in initial pancreatic cancer, leading to a more accurate clinical staging and a more rational therapeutic decision-making. [18F]AlF-NOTA-FAPI−04 PET/CT should be considered a useful diagnostic tool for initial staging of pancreatic cancer. Accurate initial staging is critical for pancreatic cancer management. Can [18F]AlF-NOTA-FAPI-04 PET/CT provide superior staging performance compared to standard contrast-enhanced CT and MRI? [18F]AlF-NOTA-FAPI-04 PET/CT demonstrated higher sensitivity and accuracy for detecting lymph node and distant metastases than CT or MRI, leading to more frequent N and M stage modifications and subsequent alterations in treatment strategy. This study supports the clinical utility of [18F]AlF-NOTA- FAPI-04 PET/CT for initial staging of pancreatic cancer, enabling more accurate disease assessment and helping to guide patients toward the most appropriate treatment plan.