FAPI-74 PET/CT Using Either 18F-AlF or Cold-Kit 68Ga 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 El Shafie, Manuel Röhrich, Paul Flechsig, Andreas Kluge, Annette Altmann, Jürgen Debus, Uwe Haberkorn, Clemens Kratochwil, 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 El Shafie, Manuel Röhrich, Paul Flechsig, Andreas Kluge, Annette Altmann, Jürgen Debus, Uwe Haberkorn, Clemens Kratochwil

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.

Keywords: FAPI PET/CT; cancer-associated fibroblasts; cold kit; lung cancer; radiation dosimetry.

© 2021 by the Society of Nuclear Medicine and Molecular Imaging.

Figures

FIGURE 1.
FIGURE 1.
Time-dependent biodistribution of 18F-FAPI-74 in normal organs and tumor.
FIGURE 2.
FIGURE 2.
(A) Maximum-intensity projections of 18F-FAPI-74 PET at 10 min, 1 h, and 3 h after injection. (B) FAPI PET/CT presents favorable discrimination between tumor and myocardium. (C–E) Some FAPI-positive lesions were confirmed by CT correlate (C), whereas additional bone lesions were only detected per FAPI PET (D and E). All highlighted arrows represent FAPI uptake with morphological correlation. p.i. = after injection.
FIGURE 3.
FIGURE 3.
(A) Maximum-intensity projections of 68Ga-FAPI-74 PET at 10 min, 1 h, and 3 h after injection. (B–E) Direct comparison of contrast-enhanced CT (B), fusion imaging (C), and FAPI PET (D). (E and F) Superior tumor delineation consecutively improved dose application to tumor volume using volumetrically modulated arc therapy. Positive FAP uptake is marked by arrows (B–F). Green outline = GTV; orange outline = clinical target volume; red outline = planning target volume. p.i. = after injection.
FIGURE 4.
FIGURE 4.
GTV automatically segmented per FAPI PET at different SUV thresholds (x = blood-pool–fold) in comparison to CT-based standard of reference.

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