Fibroblast Activation Protein-Directed Imaging Outperforms 18 F-FDG PET/CT in Malignant Mesothelioma: A Prospective, Single-Center, Observational Trial.

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 68 Ga-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 68 Ga-FAPI46 PET observational trial. All patients underwent 68 Ga-FAPI46 PET/CT, contrast-enhanced CT, and 18 F-FDG PET/CT. The primary study endpoint was the association of 68 Ga-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 18 F-FDG PET/CT. Datasets were interpreted by 2 masked readers. Results: The primary endpoint was met, and the association between 68 Ga-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). 68 Ga-FAPI46 and 18 F-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 68 Ga-FAPI46 than 18 F-FDG specificity (81.1% vs. 36.8%) and positive predictive value (87.5% vs. 66.2%). Conclusion: We confirm an association of 68 Ga-FAPI46 uptake and histopathologic FAP expression in mesothelioma patients. Additionally, we report high sensitivity and superior specificity and positive predictive value for 68 Ga-FAPI46 versus 18 F-FDG.