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 ⁶⁸Ga-FAP-2286 to detect primary and metastatic lesions in patients with various types of cancer, compared with ¹⁸F-FDG and ⁶⁸Ga-FAP-2286. Methods: Sixty-four patients with 15 types of cancer underwent ⁶⁸Ga-FAP-2286 PET/CT for initial assessment or detection of recurrence. For comparison, 63 patients underwent paired ⁶⁸Ga-FAP-2286 and ¹⁸F-FDG PET/CT and 19 patients underwent paired ⁶⁸Ga-FAP-2286 and ⁶⁸Ga-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 ⁶⁸Ga-FAP-2286 was significantly higher than that of ¹⁸F-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 ⁶⁸Ga-FAP-2286 PET/CT, whereas 9 of the 46 lesions could not be visualized by ¹⁸F-FDG PET/CT. The lesion detection rate of ⁶⁸Ga-FAP-2286 PET/CT was superior to that of ¹⁸F-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). ⁶⁸Ga-FAP-2286 yielded tumor uptake and lesion detection rates similar to those of ⁶⁸Ga-FAPI-46 in a subcohort of 19 patients. Conclusion: ⁶⁸Ga-FAP-2286 is a promising FAP-inhibitor derivative for safe cancer diagnosis, staging, and restaging. It may be a better alternative to ¹⁸F-FDG for the cancer types that exhibit low-to-moderate uptake of ¹⁸F-FDG, which include gastric, pancreatic, and hepatic cancers. In addition, ⁶⁸Ga-FAP-2286 and ⁶⁸Ga-FAPI-46 yielded comparable clinical results.

PET 成像以癌症相关成纤维细胞表面的成纤维细胞激活蛋白 (FAP) 为目标，已取得了有希望的肿瘤诊断结果。与小分子 FAP 抑制剂 (FAPI) 系列 (FAPI-04/46) 相比，FAP-2286 含有环肽作为 FAP 结合基序，可优化肿瘤保留。本研究的目的是评估^{68 Ga-FAP-2286 与18} F-FDG 和⁶⁸ Ga-FAP-2286相比，检测各种类型癌症患者的原发性和转移性病变的诊断准确性。方法： 64 名患有 15 种癌症的患者接受了⁶⁸ Ga-FAP-2286 PET/CT 进行初步评估或检测复发。为了进行比较，63 名患者接受了配对的⁶⁸ Ga-FAP-2286 和¹⁸ F-FDG PET/CT，19 名患者接受了配对的⁶⁸ Ga-FAP-2286 和⁶⁸ Ga-FAPI-46 PET/CT。病变摄取被量化为 SUV _max和肿瘤与背景的比率。Wilcoxon 配对符号秩检验用于比较 PET 模式之间的 SUV _max，McNemar 检验用于比较病变可检测性。结果：原发肿瘤中⁶⁸ Ga-FAP-2286的摄取显着高于^{18 F-FDG（中位 SUV} _max，11.1 vs. 6.9；P < 0.001），淋巴结转移灶（中位 SUV _max，10.6 vs. 6.2） ; P < 0.001) 和远处转移，从而提高图像对比度和病变可检测性。^{所有原发性肿瘤 (46/46) 通过68} Ga-FAP-2286 PET/CT均清晰可见，而¹⁸ F-FDG PET/CT无法显示 46 个病灶中的 9 个。对于受累淋巴结，⁶⁸ Ga-FAP-2286 PET/CT的病灶检出率优于^{18 F-FDG PET/CT（98% [105/107] vs. 85% [91/107]，} P = 0.001）以及骨和内脏转移（95% [162/171] vs. 67% [114/171]，P < 0.001）。在 19 名患者的亚组中，^{68 Ga-FAP-2286 产生的肿瘤摄取和病变检出率与68} Ga-FAPI-46相似。结论： ⁶⁸ Ga-FAP-2286 是一种有前景的 FAP 抑制剂衍生物，可用于安全的癌症诊断、分期和再分期。^对于18 F-FDG 摄取量低至中度的癌症类型（包括胃癌、胰腺癌和肝癌），它可能是¹⁸ F-FDG的更好替代品。此外，⁶⁸ Ga-FAP-2286 和⁶⁸Ga-FAPI-46 产生了可比的临床结果。