FAPI-74 PET/CT Using Either<sup>18</sup>F-AlF or Cold-Kit<sup>68</sup>Ga Labeling: Biodistribution, Radiation Dosimetry, and Tumor Delineation in Lung Cancer Patients
Frederik L. Giesel, Sebastian Adeberg, Mustafa Syed, Thomas Lindner, Luis David Jiménez‐Franco, Eleni Mavriopoulou, Fabian Staudinger, Eric Tonndorf‐Martini, Sebastian Regnery, Stefan Rieken, Rami A. El Shafie, Manuel Röhrich, Paul Flechsig, Andreas Kluge, Annette Altmann, Jürgen Debus, Uwe Haberkorn, Clemens Kratochwil
Abstract
<sup>68</sup>Ga-fibroblast activation protein inhibitors (FAPIs) 2, 4, and 46 have already been proposed as promising PET tracers. However, the short half-life of <sup>68</sup>Ga (68 min) creates problems with manufacture and delivery. <sup>18</sup>F (half-life, 110 min) labeling would result in a more practical large-scale production, and a cold-kit formulation would improve the spontaneous availability. The NOTA chelator ligand FAPI-74 can be labeled with both <sup>18</sup>F-AlF and <sup>68</sup>Ga. Here, we describe the in vivo evaluation of <sup>18</sup>F-FAPI-74 and a proof of mechanism for <sup>68</sup>Ga-FAPI-74 labeled at ambient temperature. <b>Methods:</b> In 10 patients with lung cancer, PET scans were acquired at 10 min, 1 h, and 3 h after administration of 259 ± 26 MBq of <sup>18</sup>F-FAPI-74. Physiologic biodistribution and tumor uptake were semiquantitatively evaluated on the basis of SUV at each time point. Absorbed doses were evaluated using OLINDA/EXM, version 1.1, and QDOSE dosimetry software with the dose calculator IDAC-Dose, version 2.1. Identical methods were used to evaluate one examination after injection of 263 MBq of <sup>68</sup>Ga-FAPI-74. <b>Results:</b> The highest contrast was achieved in primary tumors, lymph nodes, and distant metastases at 1 h after injection, with an SUV<sub>max</sub> of more than 10. The effective dose per a 100-MBq administered activity of <sup>18</sup>F-FAPI-74 was 1.4 ± 0.2 mSv, and for <sup>68</sup>Ga-FAPI-74 it was 1.6 mSv. Thus, the radiation burden of a diagnostic <sup>18</sup>F-FAPI-74 PET scan is even lower than that of PET scans with <sup>18</sup>F-FDG and other <sup>18</sup>F tracers; <sup>68</sup>Ga-FAPI-74 is comparable to other <sup>68</sup>Ga ligands. FAPI PET/CT supported target volume definition for guiding radiotherapy. <b>Conclusion:</b> The high contrast and low radiation burden of FAPI-74 PET/CT favor multiple clinical applications. Centralized large-scale production of <sup>18</sup>F-FAPI-74 or decentralized cold-kit labeling of <sup>68</sup>Ga-FAPI-74 allows flexible routine use.