PET Imaging of Fibroblast Activation Protein in Various Types of Cancer Using<sup>68</sup>Ga-FAP-2286: Comparison with<sup>18</sup>F-FDG and<sup>68</sup>Ga-FAPI-46 in a Single-Center, Prospective Study
Yizhen Pang, Liang Zhao, Tinghua Meng, Weizhi Xu, Qin Lin, Hua Wu, Jingjing Zhang, Xiaoyuan Chen, Long Sun, Haojun Chen
Abstract
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 5 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.