Fibroblast-Activation Protein PET and Histopathology in a Single-Center Database of 324 Patients and 21 Tumor Entities

Abstract

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

Keywords: FAPI; PET; oncology; staging; theranostic.