Frederik L Giesel 1, Sebastian Adeberg 2 3 4 5, Mustafa Syed 2 4, Thomas Lindner 1, Luis David Jiménez-Franco 6, Eleni Mavriopoulou 1, Fabian Staudinger 1, Eric Tonndorf-Martini 2 4, Sebastian Regnery 2 4, Stefan Rieken 2 5 7, Rami El Shafie 2 5, Manuel Röhrich 1, Paul Flechsig 1, Andreas Kluge 6, Annette Altmann 1, Jürgen Debus 2 3 4 5, Uwe Haberkorn 8 9, Clemens Kratochwil 1

Abstract: 68Ga-fibroblast activation protein inhibitors (FAPIs) 2, 4, and 46 have already been proposed as promising PET tracers. However, the short half-life of 68Ga (68 min) creates problems with manufacture and delivery. 18F (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 18F-AlF and 68Ga. Here, we describe the in vivo evaluation of 18F-FAPI-74 and a proof of mechanism for 68Ga-FAPI-74 labeled at ambient temperature.

Methods: 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 18F-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 68Ga-FAPI-74.

Results: The highest contrast was achieved in primary tumors, lymph nodes, and distant metastases at 1 h after injection, with an SUVmax of more than 10. The effective dose per a 100-MBq administered activity of 18F-FAPI-74 was 1.4 ± 0.2 mSv, and for 68Ga-FAPI-74 it was 1.6 mSv. Thus, the radiation burden of a diagnostic 18F-FAPI-74 PET scan is even lower than that of PET scans with 18F-FDG and other 18F tracers; 68Ga-FAPI-74 is comparable to other 68Ga ligands. FAPI PET/CT supported target volume definition for guiding radiotherapy.

Conclusion: The high contrast and low radiation burden of FAPI-74 PET/CT favor multiple clinical applications. Centralized large-scale production of 18F-FAPI-74 or decentralized cold-kit labeling of 68Ga-FAPI-74 allows flexible routine use.

Affiliations:

  1. Department of Nuclear Medicine, University Hospital Heidelberg, Heidelberg, Germany.
  2. Heidelberg Institute of Radiation Oncology, Heidelberg, Germany.
  3. Heidelberg Ion-Beam Therapy Center, Heidelberg, Germany.
  4. Department of Radiation Oncology, University Hospital Heidelberg, Heidelberg, Germany.
  5. Clinical Cooperation Unit Radiation Oncology, German Cancer Research Center, Heidelberg, Germany.
  6. ABX-CRO Advanced Pharmaceutical Services Forschungsgesellschaft mbH, Dresden, Germany.
  7. Department of Radiation Oncology, University Hospital Göttingen, Göttingen, Germany; and.
  8. Department of Nuclear Medicine, University Hospital Heidelberg, Heidelberg, Germany uwe.haberkorn@med.uni-heidelberg.de.
  9. Clinical Cooperation Unit Nuclear Medicine, German Cancer Research Center, Heidelberg, Germany.