Fibroblast activation protein positron emission tomography and histopathology in a single-center database of 324 patients and 21 tumor entities.

Rationale: We present an overview of our prospective fibroblast activation protein inhibitors (FAPI) registry study across a 3-year period, with head-to-head comparison of tumor uptake in 68 Ga-FAPI and 18 F-FDG PET, as well as FAP immunohistochemistry. Methods: This is an interim analysis of the ongoing 68 Ga-FAPI PET prospective observational trial at our Department. Patients who underwent clinical imaging with 68 Ga-FAPI PET between October 2018 and October 2021 were included. Tracer uptake for tumor lesions was quantified by SUV max and for normal organs by SUVmean. PET tumor volume (40% isocontour) and tumor-to-background ratios (TBR) were calculated. Correlation between SUV max and FAP staining in tissue samples was analyzed. Results: 324 patients with 21 different tumor entities underwent 68 Ga-FAPI imaging; 237 patients additionally received 18 F-FDG PET. The most common tumor entities were sarcoma (131/324, 40%), pancreatic carcinoma (67/324, 21%), and primary tumors of the brain (22/324, 7%). Mean primary tumor SUV max was significantly higher for 68 Ga-FAPI than 18 F-FDG among pancreatic cancers (13.2 vs. 6.1, p<0.001) and sarcoma (14.3 vs. 9.4, p<0.001), and the same was true for mean SUV max in metastatic lesions of pancreatic cancers (9.4 vs. 5.5, p<0.001). Mean primary tumor TBRmax was significantly higher for 68 Ga-FAPI than 18 F-FDG across several tumor entities, most prominently pancreatic cancers (14.7 vs. 3.0, p<0.001) and sarcoma (17.3 vs. 4.7, p<0.001). Compared to 18 F-FDG, 68 Ga-FAPI showed superior detection for locoregional disease in sarcoma (52 vs. 48 total regions detected) as well as for distant metastatic disease in both, sarcoma (137 vs. 131) and pancreatic cancer (65 vs. 57), respectively. Among 61 histopathology samples, there was a positive correlation between 68 Ga-FAPI SUV max and overall FAP immunohistochemistry score (r=0.352, P = 0.005). Conclusion: 68 Ga-FAPI demonstrates higher absolute uptake in pancreatic cancers and sarcoma, as well as higher tumor-to-background uptake along with improved tumor detection for pancreatic cancers, sarcoma, and other tumor entities when compared to 18 F-FDG. 68 Ga-FAPI is a new tool for tumor staging with theranostic potential.