<sup>68</sup>Ga-Labeled Fibroblast Activation Protein Inhibitor (<sup>68</sup>Ga-FAPI) PET for Pancreatic Adenocarcinoma: Data from the<sup>68</sup>Ga-FAPI PET Observational Trial
Lukas Kessler, Nader Hirmas, Kim M. Pabst, Rainer Hamacher, Justin Ferdinandus, Benedikt M. Schaarschmidt, Aleksandar Milošević, Michael Nader, Lale Umutlu, Waldemar Uhl, Anke Reinacher‐Schick, Céline Lugnier, David P. Witte, Marco Niedergethmann, Ken Herrmann, Wolfgang P. Fendler, Jens T. Siveke
Abstract
The fibroblast activation protein (FAP) is highly expressed on carcinoma-associated fibroblasts in the stroma of pancreatic cancer and thus is a promising target for imaging and therapy. Preliminary data on PET imaging with radiolabeled FAP inhibitors (FAPIs) demonstrate superior tumor detection. Here we assess the accuracy of FAP-directed PET in patients with pancreatic cancer. <b>Methods:</b> Of 64 patients with suspected or proven pancreatic cancer, 62 (97%) were included in the data analysis of the <sup>68</sup>Ga-FAPI PET observational trial (NCT04571086). All of these patients underwent contrast-enhanced CT, and 38 patients additionally underwent <sup>18</sup>F-FDG PET. The primary study endpoint was the association of <sup>68</sup>Ga-FAPI PET uptake intensity and histopathologic FAP expression. Secondary endpoints were detection rate, diagnostic performance, interreader reproducibility, and change in management. Datasets were interpreted by 2 masked readers. <b>Results:</b> The primary endpoint was met: The association between <sup>68</sup>Ga-FAPI SUV<sub>max</sub> and histopathologic FAP expression was significant (Spearman <i>r</i>, 0.48; <i>P</i> = 0.04). For histopathology-validated lesions, <sup>68</sup>Ga-FAPI PET showed high sensitivity and positive predictive values (PPVs) on per-patient (sensitivity, 100%; PPV, 96.3%) and per-region (sensitivity, 100%; PPV, 97.0%) bases. In a head-to-head comparison versus <sup>18</sup>F-FDG or contrast-enhanced CT, <sup>68</sup>Ga-FAPI detected more tumor on a per-lesion (84.7% vs. 46.5% vs. 52.9%), per-patient (97.4% vs. 73.7% vs. 92.1%), or per-region (32.6% vs. 18.8% vs. 23.7%) basis, respectively. <sup>68</sup>Ga-FAPI PET readers showed substantial overall agreement on the basis of the Fleiss κ: primary κ, 0.77 (range, 0.66–0.88). Minor and major changes in clinical management occurred in 5 patients (8.4%) after <sup>68</sup>Ga-FAPI PET. <b>Conclusion:</b> We confirmed an association of <sup>68</sup>Ga-FAPI PET SUV<sub>max</sub> and histopathologic FAP expression in pancreatic cancer patients. Additionally, we found high detection rate and diagnostic accuracy, superior to those of <sup>18</sup>F-FDG PET/CT. <sup>68</sup>Ga-FAPI might become a powerful diagnostic tool for pancreatic cancer work-up.