Fibroblast Activation Protein–Targeted PET/CT with<sup>18</sup>F-Fibroblast Activation Protein Inhibitor-74 for Evaluation of Gastrointestinal Cancer: Comparison with<sup>18</sup>F-FDG PET/CT
Weizhi Xu, Jiayu Cai, Peng Tianxing, Tinghua Meng, Yizhen Pang, Long Sun, Hua Wu, Jingjing Zhang, Xiaoyuan Chen, Haojun Chen
Abstract
Fibroblast activation protein is overexpressed in the stroma of several cancer types. <sup>18</sup>F-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 <sup>18</sup>F-FAPI-74 for PET imaging of gastrointestinal cancer has not been systematically investigated. Herein, we investigated the diagnostic accuracy of <sup>18</sup>F-FAPI-74 (<sup>18</sup>F-LNC1005) PET/CT in gastric, liver, and pancreatic cancers and compared the results with those of <sup>18</sup>F-FDG PET/CT. <b>Methods:</b> This prospective study analyzed patients with confirmed gastric, liver, or pancreatic malignancies who underwent concurrent <sup>18</sup>F-FDG and <sup>18</sup>F-FAPI-74 PET/CT between June 2022 and December 2022. PET/CT findings were confirmed by histopathology or radiographic follow-up. <sup>18</sup>F-FDG and <sup>18</sup>F-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. <b>Results:</b> 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, <sup>18</sup>F-FAPI-74 PET/CT showed higher sensitivity than did <sup>18</sup>F-FDG in the detection of primary tumors (gastric cancer, 88% [22/25] vs. 60% [15/25], <i>P</i> = 0.016; liver cancer, 100% [22/22] vs. 82% [18/22], <i>P</i> = 0.125; pancreatic cancer, 100% [22/22] vs. 86% [19/22], <i>P</i> = 0.250), local recurrence (92% [23/25] vs. 56% [14/25]; <i>P</i> = 0.021), involved lymph nodes (71% [41/58] vs. 40% [23/58]; <i>P</i> < 0.001), and bone and visceral metastases (98% [350/358] vs. 47% [168/358]; <i>P</i> < 0.001). Compared with <sup>18</sup>F-FDG, <sup>18</sup>F-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. <b>Conclusion:</b><sup>18</sup>F-FAPI-74 PET/CT is superior to <sup>18</sup>F-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.