The fibroblast activation protein (FAP) is highly expressed in tumor and stromal cells of mesothelioma and thus is an interesting imaging and therapeutic target. Previous data on PET imaging with radiolabeled FAP inhibitors (FAPIs) suggest high potential for superior tumor detection. Here, we report the data of a large malignant pleural mesothelioma cohort within a ⁶⁸Ga-FAPI46 PET observational trial (NCT04571086). Methods: Of 43 eligible patients with suspected or proven malignant mesothelioma, 41 could be included in the data analysis of the ⁶⁸Ga-FAPI46 PET observational trial. All patients underwent ⁶⁸Ga-FAPI46 PET/CT, contrast-enhanced CT, and ¹⁸F-FDG PET/CT. The primary study endpoint was the association of ⁶⁸Ga-FAPI46 PET uptake intensity and histopathologic FAP expression. Furthermore, secondary endpoints were detection rate and sensitivity, specificity, and positive and negative predictive values as compared with ¹⁸F-FDG PET/CT. Datasets were interpreted by 2 masked readers. Results: The primary endpoint was met, and the association between ⁶⁸Ga-FAPI46 SUV_max or SUV_peak and histopathologic FAP expression was significant (SUV_max: r = 0.49, P = 0.037; SUV_peak: r = 0.51, P = 0.030).⁶⁸Ga-FAPI46 and ¹⁸F-FDG showed similar sensitivity by histopathologic validation on a per-patient (100.0% vs. 97.3%) and per region (98.0% vs. 95.9%) basis. Per-region analysis revealed higher ⁶⁸Ga-FAPI46 than ¹⁸F-FDG specificity (81.1% vs. 36.8%) and positive predictive value (87.5% vs. 66.2%). Conclusion: We confirm an association of ⁶⁸Ga-FAPI46 uptake and histopathologic FAP expression in mesothelioma patients. Additionally, we report high sensitivity and superior specificity and positive predictive value for ⁶⁸Ga-FAPI46 versus ¹⁸F-FDG.

成纤维细胞激活蛋白（FAP）在间皮瘤的肿瘤和基质细胞中高表达，因此是一个有趣的成像和治疗靶点。先前使用放射​​性标记 FAP 抑制剂 (FAPI) 进行 PET 成像的数据表明，其具有出色的肿瘤检测潜力。在这里，我们报告了⁶⁸ Ga-FAPI46 PET 观察试验 (NCT04571086) 中大型恶性胸膜间皮瘤队列的数据。方法：在 43 名符合条件的疑似或确诊恶性间皮瘤患者中，41 名可纳入⁶⁸ Ga-FAPI46 PET 观察性试验的数据分析。所有患者均接受⁶⁸ Ga-FAPI46 PET/CT、增强 CT 和¹⁸ F-FDG PET/CT。主要研究终点是⁶⁸ Ga-FAPI46 PET 摄取强度与组织病理学 FAP 表达的关联。此外，次要终点是与¹⁸ F-FDG PET/CT 相比的检出率、灵敏度、特异性以及阳性和阴性预测值。数据集由 2 位蒙面读者解读。结果：达到了主要终点，并且⁶⁸ Ga-FAPI46 SUV _max或 SUV_峰值与组织病理学 FAP 表达之间存在显着相关性（SUV _max ： r = 0.49， P = 0.037；SUV_峰值： r = 0.51， P = 0.030） 。通过针对每位患者（100.0% 与 97.3%）和每个区域（98.0% 与 95.9%）的组织病理学验证， ⁶⁸ Ga-FAPI46 和¹⁸ F-FDG 显示出相似的敏感性。按区域分析显示⁶⁸ Ga-FAPI46 比¹⁸ F-FDG 特异性更高 (81.1% vs. 36.8%）和阳性预测值（87.5% vs. 66.2%）。结论：我们证实间皮瘤患者中⁶⁸ Ga-FAPI46 摄取与组织病理学 FAP 表达之间存在关联。此外，我们报告⁶⁸ Ga-FAPI46 与¹⁸ F-FDG 相比具有高灵敏度、卓越的特异性和阳性预测值。