PET imaging of fibroblast activation protein in various types of cancers by using 68 Ga-FAP-2286: Comparison with 18 F-FDG and 68 Ga-FAPI-46 in a single-center, prospective study.

PET imaging targeting 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 the 68 Ga-FAP-2286 to detect the primary and metastatic lesions in patients with various types of cancer, compared with 18 F-fluorodeoxyglucose (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 recurrence detection. For comparative purposes, 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 imaging. Lesion uptake was quantified as the maximum standardized uptake value (SUV max ) and tumor-to-background ratio. The Wilcoxon matched-pairs signed-rank test was used to compare SUV max values, and McNemar's test was used to compare the lesion detectability between PET modalities. Results: The 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, resulted in improved image contrast and higher 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 via 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), bone and visceral metastases (95 % [162/171] vs. 67 % [114/171], P < 0.001). 68 Ga-FAP-2286 yielded similar tumor uptake and lesion detection rates as compared with 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 including gastric, pancreatic, and liver cancers. In addition, 68 Ga-FAP-2286 and 68 Ga-FAPI-46 yielded comparable clinical results.