Clinical Value of [⁶⁸Ga]Ga-FAPI-46 PET/CT Versus [¹⁸F]FDG PET/CT for Primary Staging of Gastroesophageal Adenocarcinoma: Results from a Prospective Northern European Trial.

Abstract

Previous studies have demonstrated promising results for radiolabeled fibroblast activation protein inhibitor (FAPI) PET/CT in gastric cancer (GC) when compared with [¹⁸F]FDG PET/CT. In this prospective clinical trial, we assessed the impact of [⁶⁸Ga]Ga-FAPI-46 PET/CT compared with [¹⁸F]FDG PET/CT and contrast-enhanced CT (ceCT) on primary staging and management of Danish patients with GC and gastroesophageal junction cancer (GEJC). Methods: Between February 8, 2024, and September 26, 2025, consecutive patients with GC or GEJC who were candidates for surgical resection and perioperative chemotherapy were included in this trial. [⁶⁸Ga]Ga-FAPI-46 PET/CT images were deidentified and presented to the treating clinicians after the trial, at which point [⁶⁸Ga]Ga-FAPI-46 PET/CT-based staging and tentative patient management were determined. Results: Twenty patients were included in the trial, including 15 (75%) with GEJC and 5 (25%) with GC; all patients were diagnosed with adenocarcinoma. For the primary tumor, [⁶⁸Ga]Ga-FAPI-46 and [¹⁸F]FDG PET/CT agreed in 18 (90%) of cases, and both modalities demonstrated a detection rate of 90% (95% CI, 68%-99%). For clinical nodal staging, ceCT detected more lymph nodes than did [⁶⁸Ga]Ga-FAPI-46 PET and [¹⁸F]FDG PET alone (81 vs. 53 vs. 44, respectively). [⁶⁸Ga]Ga-FAPI-46 PET did not detect additional lymph nodes beyond those detected with ceCT. Despite detecting fewer lymph nodes overall, [¹⁸F]FDG PET identified 6 additional lymph nodes in 5 patients, resulting in clinical nodal upstaging in 4 cases (20%) compared with both [⁶⁸Ga]Ga-FAPI-46 PET and ceCT. [⁶⁸Ga]Ga-FAPI-46 PET would have led to clinical metastatic upstaging in 4 patients (20%) because of the identification of potential distant metastases (1 peritoneal and 3 liver metastases), which would have resulted in a change in recommended patient management from curative-intent to palliative treatment in 3 patients (15%). Conclusion: The primary clinical value of [⁶⁸Ga]Ga-FAPI-46 PET was its ability to detect distant metastases that were negative on [¹⁸F]FDG PET and ceCT, potentially impacting patient management. There were no obvious advantages in the evaluation of primary tumor and regional lymph nodes. Although the study population is relatively small and mostly consists of patients with GEJC, this study represents the first prospective investigation of consecutive patients in a well-defined, clinical northern European setting and indicates potential future roles for [⁶⁸Ga]Ga-FAPI-46 PET in GC and GEJC.