Fibroblast activation protein-α (FAP) is often highly expressed by sarcoma cells and by sarcoma-associated fibroblasts in the tumor microenvironment. This makes it a promising target for imaging and therapy. The level of FAP expression and the diagnostic value of ⁶⁸Ga-FAP inhibitor (FAPI) PET for sarcoma subtypes are unknown. We assessed the diagnostic performance and accuracy of ⁶⁸Ga-FAPI PET in various bone and soft-tissue sarcomas. Potential eligibility for FAP-targeted radiopharmaceutical therapy (FAP-RPT) was evaluated. Methods: This prospective observational trial enrolled 200 patients with bone and soft-tissue sarcoma who underwent ⁶⁸Ga-FAPI PET/CT and ¹⁸F-FDG PET/CT (186/200, or 93%) for staging or restaging. The number of lesions detected and the uptake (SUV_max) of the primary tumor, lymph nodes, and visceral and bone metastases were analyzed. The Wilcoxon test was used for semiquantitative assessment. The association of ⁶⁸Ga-FAPI uptake intensity, histopathologic grade, and FAP expression in sarcoma biopsy samples was analyzed using Spearman r correlation. The impact of ⁶⁸Ga-FAPI PET on clinical management was investigated using questionnaires before and after PET/CT. Eligibility for FAP-RPT was defined by an SUV_max greater than 10 for all tumor regions. Results: ⁶⁸Ga-FAPI uptake was heterogeneous among sarcoma subtypes. The 3 sarcoma entities with the highest uptake (mean SUV_max ± SD) were solitary fibrous tumor (24.7 ± 11.9), undifferentiated pleomorphic sarcoma (18.8 ± 13.1), and leiomyosarcoma (15.2 ± 10.2). Uptake of ⁶⁸Ga-FAPI versus ¹⁸F-FDG was significantly higher in low-grade sarcomas (10.4 ± 8.5 vs. 7.0 ± 4.5, P = 0.01) and in potentially malignant intermediate or unpredictable sarcomas without a World Health Organization grade (not applicable [NA]; 22.3 ± 12.5 vs. 8.5 ± 10.0, P = 0.0004), including solitary fibrous tumor. The accuracy, as well as the detection rates, of ⁶⁸Ga-FAPI was higher than that of ¹⁸F-FDG in low-grade sarcomas (accuracy, 92.2 vs. 80.0) and NA sarcomas (accuracy, 96.9 vs. 81.9). ⁶⁸Ga-FAPI uptake and the histopathologic FAP expression score (n = 89) were moderately correlated (Spearman r = 0.43, P < 0.0002). Of 138 patients, 62 (45%) with metastatic sarcoma were eligible for FAP-RPT. Conclusion: In patients with low-grade and NA sarcomas, ⁶⁸Ga-FAPI PET demonstrates uptake, detection rates, and accuracy superior to those of ¹⁸F-FDG PET. ⁶⁸Ga-FAPI PET criteria identified eligibility for FAP-RPT in about half of sarcoma patients.

成纤维细胞激活蛋白-α (FAP) 通常在肿瘤微环境中的肉瘤细胞和肉瘤相关成纤维细胞中高度表达。这使其成为成像和治疗的有希望的目标。 FAP 表达水平和⁶⁸ Ga-FAP 抑制剂 (FAPI) PET 对肉瘤亚型的诊断价值尚不清楚。我们评估了⁶⁸ Ga-FAPI PET 在各种骨和软组织肉瘤中的诊断性能和准确性。评估了 FAP 靶向放射性药物治疗 (FAP-RPT) 的潜在资格。方法：这项前瞻性观察试验纳入了 200 名骨和软组织肉瘤患者，他们接受了⁶⁸ Ga-FAPI PET/CT 和¹⁸ F-FDG PET/CT（186/200，或 93%）进行分期或再分期。分析检测到的病灶数量以及原发肿瘤、淋巴结、内脏和骨转移灶的摄取（SUV _max ）。 Wilcoxon 检验用于半定量评估。使用Spearman r相关性分析肉瘤活检样本中⁶⁸ Ga-FAPI 摄取强度、组织病理学分级和FAP 表达的关联。通过 PET/CT 前后的问卷调查，研究⁶⁸ Ga-FAPI PET 对临床管理的影响。 FAP-RPT 的资格定义为所有肿瘤区域的 SUV_最大值大于 10。结果：⁶⁸ Ga-FAPI 摄取在肉瘤亚型之间存在异质性。摄取率最高的 3 个肉瘤实体（平均 SUV _max ± SD）是孤立性纤维瘤 (24.7 ± 11.9)、未分化多形性肉瘤 (18.8 ± 13.1) 和平滑肌肉瘤 (15.2 ± 10.2)。低级别肉瘤中⁶⁸ Ga-FAPI的摄取量显着高于^{18 F-FDG（10.4 ± 8.5 对比 7.0 ± 4.5，} P = 0.01）以及没有世界卫生组织分级的潜在恶性中间或不可预测的肉瘤（不适用） [NA]；22.3 ± 12.5 vs. 8.5 ± 10.0，P = 0.0004)，包括孤立性纤维瘤。在低级别肉瘤（准确度，92.2 vs. 80.0）和 NA 肉瘤（准确度，96.9 vs. 81.9）中，⁶⁸ Ga-FAPI的准确度和检出率均高于^{18 F-FDG。 68} Ga-FAPI 摄取和组织病理学 FAP 表达评分 ( n = 89) 呈中度相关 (Spearman r = 0.43, P < 0.0002)。在 138 名患者中，62 名（45%）患有转移性肉瘤符合 FAP-RPT 条件。结论：在低度恶性和 NA 肉瘤患者中，⁶⁸ Ga-FAPI PET 的摄取率、检出率和准确度均优于¹⁸ F-FDG PET。⁶⁸ Ga-FAPI PET 标准确定了约一半肉瘤患者是否有资格接受 FAP-RPT。