Fibroblast Activation Protein–Targeted PET/CT with18F-Fibroblast Activation Protein Inhibitor-74 for Evaluation of Gastrointestinal Cancer: Comparison with18F-FDG PET/CT

Fibroblast activation protein is overexpressed in the stroma of several cancer types. ¹⁸F-fibroblast activation protein inhibitor (FAPI)–74 is a PET tracer with high selectivity for fibroblast activation protein and has shown high accumulation in human tumors in clinical studies. However, the use of ¹⁸F-FAPI-74 for PET imaging of gastrointestinal cancer has not been systematically investigated. Herein, we investigated the diagnostic accuracy of ¹⁸F-FAPI-74 (¹⁸F-LNC1005) PET/CT in gastric, liver, and pancreatic cancers and compared the results with those of ¹⁸F-FDG PET/CT. Methods: This prospective study analyzed patients with confirmed gastric, liver, or pancreatic malignancies who underwent concurrent ¹⁸F-FDG and ¹⁸F-FAPI-74 PET/CT between June 2022 and December 2022. PET/CT findings were confirmed by histopathology or radiographic follow-up. ¹⁸F-FDG and ¹⁸F-FAPI-74 uptake and tumor-to-background ratios were compared using the Wilcoxon signed-rank test. The McNemar test was used to compare the diagnostic accuracy of the 2 scans. Results: Our cohort consisted of 112 patients: 49 with gastric cancer, 39 with liver cancer, and 24 with pancreatic cancer. Among them, 69 patients underwent PET/CT for initial staging and 43 for recurrence detection. Regarding lesion-based diagnostic accuracy, ¹⁸F-FAPI-74 PET/CT showed higher sensitivity than did ¹⁸F-FDG in the detection of primary tumors (gastric cancer, 88% [22/25] vs. 60% [15/25], P = 0.016; liver cancer, 100% [22/22] vs. 82% [18/22], P = 0.125; pancreatic cancer, 100% [22/22] vs. 86% [19/22], P = 0.250), local recurrence (92% [23/25] vs. 56% [14/25]; P = 0.021), involved lymph nodes (71% [41/58] vs. 40% [23/58]; P < 0.001), and bone and visceral metastases (98% [350/358] vs. 47% [168/358]; P < 0.001). Compared with ¹⁸F-FDG, ¹⁸F-FAPI-74 PET/CT upstaged 17 patients' TNM staging among all treatment-naïve patients (17/69, 25%) and changed the clinical management of 4 patients (4/43, 9%) in whom recurrence or metastases were detected. Conclusion:¹⁸F-FAPI-74 PET/CT is superior to ¹⁸F-FDG PET/CT in detecting primary tumors, local recurrence, lymph node involvement, and bone and visceral metastases in gastric, pancreatic, and liver cancers, with higher uptake in most primary and metastatic lesions.