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-tohead 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 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 68 Ga-FAPI imaging; 237 patients additionally received 18 F-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 68 Ga-FAPI than 18 F-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 68 Ga-FAPI than 18 F-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 18

Comparison of Baseline68Ga-FAPI and18F-FDG PET/CT for Prediction of Response and Clinical Outcome in Patients with Unresectable Hepatocellular Carcinoma Treated with PD-1 Inhibitor and Lenvatinib

“…The communication is complicated between tumor metabolism and heterogeneous stromal components in the tumor microenvironment. Previous studies showed that 68 Ga-FAPI PET uptake and distribution strongly correlated with FAP expression characterized by immunohistochemistry in tumor tissues (10,16). FAP-positive cancerassociated fibroblast subsets contribute to immunosuppression through multiple pathways, including assisting differentiation of monocytes to M2-like macrophages, secreting chemokine (C-X-C motif) ligand 12, enhancing recruitment of myeloid-derived suppressor cells, and promoting generation of regulatory T cells (17)(18)(19)(20).…”

Design, Preclinical Evaluation, and Clinical Translation of68Ga-FAPI-LM3, a Heterobivalent Molecule for PET Imaging of Nasopharyngeal Carcinoma

“…FAP is expressed in a wide range of tumor types, making it a promising target for cancer imaging and radionuclide therapy in recent years ( 4 , 5 ). Apart from neuroendocrine tumors, most other cancers, such as NPC, thyroid cancer, and breast cancer, express SSTR2 ( 9 , 14 , 22 , 23 ).…”

Preclinical evaluation and first-in-human study of Al18F-FAP-NUR for PET imaging cancer-associated fibroblasts

“…The quinoline-based small molecule inhibitors that target FAP, known as FAPIs (including FAPI-04 [6,11], FAPI-46 [12,13], and FAPI-74 [14,15]), labeled with 68 Ga for use in positron emission tomography (PET) scans, have exhibited promising outcomes in the diagnosis of various types of cancers [15][16][17]. These tracers exhibit a high a nity for FAP and demonstrate enhanced selectivity towards tumors compared to normal tissues.…”