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.
(© 2024 by the Society of Nuclear Medicine and Molecular Imaging.)