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

• Published in: Journal of Nuclear Medicine Vol. 64; no. 5; pp. 711 - 716
• Main Authors: Hirmas, Nader, Hamacher, Rainer, Sraieb, Miriam, Ingenwerth, Marc, Kessler, Lukas, Pabst, Kim M, Barbato, Francesco, Lueckerath, Katharina, Kasper, Stefan, Nader, Michael, Schildhaus, Hans-Ulrich, Kesch, Claudia, von Tresckow, Bastian, Hanoun, Christine, Hautzel, Hubertus, Aigner, Clemens, Glas, Martin, Stuschke, Martin, Kümmel, Sherko, Harter, Philipp, Lugnier, Celine, Uhl, Waldemar, Niedergethmann, Marco, Hadaschik, Boris, Grünwald, Viktor, Siveke, Jens T, Herrmann, Ken, Fendler, Wolfgang P
• Format: Journal Article
• Language: English
• Published: United States Society of Nuclear Medicine 01.05.2023
• Subjects: Brain tumors; Cancer; Fibroblasts; Fluorine isotopes; Fluorodeoxyglucose F18; Gallium Radioisotopes; Histopathology; Humans; Immunohistochemistry; Lesions; Medical imaging; Metastases; Metastasis; Neuroimaging; Observational Studies as Topic; Pancreatic cancer; Pancreatic Neoplasms; Positron emission; Positron emission tomography; Positron Emission Tomography Computed Tomography; Prospective Studies; Proteins; Quinolines; Sarcoma; Soft Tissue Neoplasms; Tumors; FAPI; theranostic; staging; PET; oncology
• ISSN: 0161-5505; 1535-5667; 2159-662X
• DOI: 10.2967/jnumed.122.264689

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 Ga-FAPI and F-FDG PET, as well as FAP immunohistochemistry. This is an interim analysis of the ongoing Ga-FAPI PET prospective observational trial at our department. Patients who underwent clinical imaging with Ga-FAPI PET between October 2018 and October 2021 were included. Tracer uptake was quantified by SUV for tumor lesions and by SUV for normal organs. PET tumor volume (40% isocontour) and tumor-to-background ratios were calculated. Correlation between SUV and FAP staining in tissue samples was analyzed. In total, 324 patients with 21 different tumor entities underwent Ga-FAPI imaging; 237 patients additionally received 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 was significantly higher for Ga-FAPI than F-FDG among pancreatic cancer (13.2 vs. 6.1, < 0.001) and sarcoma (14.3 vs. 9.4, < 0.001), and the same was true for mean SUV in metastatic lesions of pancreatic cancer (9.4 vs. 5.5, < 0.001). Mean primary tumor maximum tumor-to-background ratio was significantly higher for Ga-FAPI than F-FDG across several tumor entities, most prominently pancreatic cancer (14.7 vs. 3.0, < 0.001) and sarcoma (17.3 vs. 4.7, < 0.001). Compared with F-FDG, Ga-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 Ga-FAPI SUV and overall FAP immunohistochemistry score ( = 0.352, = 0.005). Ga-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 F-FDG. Ga-FAPI is a new tool for tumor staging with theranostic potential.