Kessler_2024_J.Nucl.Med_65_1188

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.