Ga-FAPI-2/4/46 have already been proposed as promising PET-tracers. However, the short half-life of 68 Ga (T1/2 68 min) creates problems with manufacture and delivery. 18 F (T1/2 110 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 18 F-AlF (Aluminum-Fluoride) and 68 Ga. Here we describe the in-vivo evaluation of 18 F-FAPI-74 and a proof-of-mechanism of 68 Ga-FAPI-74 labeled at ambient temperature. Methods: In ten patients with lung cancer PET-scans were acquired at 10 min, 1h and 3h after administration of 259±26 MBq 18 F-FAPI-74. Physiological biodistribution and tumor uptake were semi-quantitatively evaluated based on SUV at each time-point. Absorbed doses were evaluated using OLINDA/EXM 1.1 and QDOSE dosimetry software with the dose calculator IDAC-Dose 2.1. Identical methods were used to evaluate one exam after injection of 263 MBq 68 Ga-FAPI-74. Results: The highest contrast was achieved 1 h p.i. in primary tumors, lymph node and distant metastases with SUVmax >10, respectively. The effective dose per 100 MBq administered activity of 18 F-FAPI-74 was 1.4±0.2 mSv and for 68 Ga-FAPI-74 it was 1.6 mSv. Thus, the radiation burden of a diagnostic 18 F-FAPI-74 PET-scan is even lower than that of PET-scans with 18 F-FDG and other 18 F-tracers; 68 Ga-FAPI-74 is comparable to other 68 Ga-ligands. FAPI-PET/CT supported target volume definition for guiding radiotherapy. Conclusion: High contrast and low radiation burden of FAPI-74 PET/CT favors multiple clinical applications. Centralized large-scale production of 18 F-FAPI-74 or decentralized cold-kit labeling of 68 Ga-FAPI-74 allows flexible routine use.

We propose a SUVmax cutoff of >16.4 from [(68)Ga]DOTATOC-PET-CT to select patients for PRRT. A T/L ratio >2.2 might present a scanner-independent criterion that enables the translation of our results to other institutions. However, the robustness of this arbitrary unit still needs to be evaluated with different PET scanners.

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