FAPI-74 PET/CT Using Either 18F-AlF or Cold-Kit 68Ga Labeling: Biodistribution, Radiation Dosimetry, and Tumor Delineation in Lung Cancer Patients

Ga-68-fibroblast activation protein inhibitors (FAPIs) 2, 4, and 46 have already been proposed as promising PET tracers. However, the short half-life of Ga-68 (68 min) creates problems with manufacture and delivery. F-18 (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 F-18-AlF and Ga-68. Here, we describe the in vivo evaluation of F-18-FAPI-74 and a proof of mechanism for Ga-68-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 F-18-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 F-18-FAPI74 was 1.4 +/- 0.2 mSv, and for Ga-68-FAPI-74 it was 1.6 mSv. Thus, the radiation burden of a diagnostic F-18-FAPI-74 PET scan is even lower than that of PET scans with F-18-FDG and other F-18 tracers; Ga-68-FAPI-74 is comparable to other Ga-68 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 F-18-FAPI-74 or decentralized cold-kit labeling of (68)GaFAPI-74 allows flexible routine use.

Automated summary

F-18-FAPI-74 shows good physiological distribution and tumor uptake in PET scans of lung cancer patients. The effective dose radiation burden of F-18-FAPI-74 is lower than that of F-18-FDG and other F-18 tracers, while Ga-68-FAPI-74 is comparable to other Ga-68 ligands.