Pang_2023_J.Nucl.Med_64_386

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 (68)Ga-FAP-2286 to detect primary and metastatic lesions in patients with various types of cancer, compared with (18)F-FDG and (68)Ga-FAP-2286. Methods: Sixty-four patients with 15 types of cancer underwent (68)Ga-FAP-2286 PET/CT for initial assessment or detection of recurrence. For comparison, 63 patients underwent paired (68)Ga-FAP-2286 and (18)F-FDG PET/CT and 19 patients underwent paired (68)Ga-FAP-2286 and (68)Ga-FAPI-46 PET/CT. Lesion uptake was quantified as SUV(max) and tumor-to-background ratio. The Wilcoxon matched-pairs signed-rank test was used to compare SUV(max) between PET modalities, and the McNemar test was used to compare lesion detectability. Results: Uptake of (68)Ga-FAP-2286 was significantly higher than that of (18)F-FDG in primary tumors (median SUV(max), 11.1 vs. 6.9; P < 0.001), lymph node metastases (median SUV(max), 10.6 vs. 6.2; P < 0.001), and distant metastases, resulting in improved image contrast and lesion detectability. All primary tumors (46/46) were clearly visualized by (68)Ga-FAP-2286 PET/CT, whereas 9 of the 46 lesions could not be visualized by (18)F-FDG PET/CT. The lesion detection rate of (68)Ga-FAP-2286 PET/CT was superior to that of (18)F-FDG PET/CT for involved lymph nodes (98% [105/107] vs. 85% [91/107], P = 0.001) and bone and visceral metastases (95% [162/171] vs. 67% [114/171], P < 0.001). (68)Ga-FAP-2286 yielded tumor uptake and lesion detection rates similar to those of (68)Ga-FAPI-46 in a subcohort of 19 patients. Conclusion: (68)Ga-FAP-2286 is a promising FAP-inhibitor derivative for safe cancer diagnosis, staging, and restaging. It may be a better alternative to (18)F-FDG for the cancer types that exhibit low-to-moderate uptake of (18)F-FDG, which include gastric, pancreatic, and hepatic cancers. In addition, (68)Ga-FAP-2286 and (68)Ga-FAPI-46 yielded comparable clinical results.