PET Imaging of Fibroblast Activation Protein in Various Types of Cancer Using Ga-FAP-2286: Comparison with F-FDG and Ga-FAPI-46 in a Single-Center, Prospective Study.

PET imaging that targets fibroblast activation protein (FAP) on the surface of cancer-associated fibroblasts has yielded promising tumor diagnostic results. FAP-2286 contains cyclic peptides as FAP-binding motifs to optimize tumor retention compared with the small-molecule FAP inhibitor (FAPI) series (FAPI-04/46). The aim of this study was to evaluate the diagnostic accuracy of Ga-FAP-2286 to detect primary and metastatic lesions in patients with various types of cancer, compared with F-FDG and Ga-FAP-2286. Sixty-four patients with 15 types of cancer underwent Ga-FAP-2286 PET/CT for initial assessment or detection of recurrence. For comparison, 63 patients underwent paired Ga-FAP-2286 and F-FDG PET/CT and 19 patients underwent paired Ga-FAP-2286 and Ga-FAPI-46 PET/CT. Lesion uptake was quantified as SUV and tumor-to-background ratio. The Wilcoxon matched-pairs signed-rank test was used to compare SUV between PET modalities, and the McNemar test was used to compare lesion detectability. Uptake of Ga-FAP-2286 was significantly higher than that of F-FDG in primary tumors (median SUV, 11.1 vs. 6.9; < 0.001), lymph node metastases (median SUV, 10.6 vs. 6.2; < 0.001), and distant metastases, resulting in improved image contrast and lesion detectability. All primary tumors (46/46) were clearly visualized by Ga-FAP-2286 PET/CT, whereas 9 of the 46 lesions could not be visualized by F-FDG PET/CT. The lesion detection rate of Ga-FAP-2286 PET/CT was superior to that of F-FDG PET/CT for involved lymph nodes (98% [105/107] vs. 85% [91/107], = 0.001) and bone and visceral metastases (95% [162/171] vs. 67% [114/171], < 0.001). Ga-FAP-2286 yielded tumor uptake and lesion detection rates similar to those of Ga-FAPI-46 in a subcohort of 19 patients. Ga-FAP-2286 is a promising FAP-inhibitor derivative for safe cancer diagnosis, staging, and restaging. It may be a better alternative to F-FDG for the cancer types that exhibit low-to-moderate uptake of F-FDG, which include gastric, pancreatic, and hepatic cancers. In addition, Ga-FAP-2286 and Ga-FAPI-46 yielded comparable clinical results.