Purpose [¹⁸F]FAPI-42 is a new fibroblast activation protein (FAP)-specific tracer used for cancer imaging. Here, we describe the optimal acquisition time and in vivo evaluation of [¹⁸F]FAPI-42 and compared intra-individual biodistribution, tumor uptake, and detection ability to [⁶⁸Ga]Ga-FAPI-04. Methods A total of 22 patients with various types of cancer received [¹⁸F]FAPI-42 whole-body positron emission tomography/computed tomography (PET/CT). Among them, 4 patients underwent PET/CT scans, including an early dynamic 20-min, static 1-h, and static 2-h scans. The in vivo biodistribution in normal organs and tumor uptake were semiquantitatively evaluated using the standardized uptake value (SUV) and tumor-to-background ratio (TBR). Furthermore, both [¹⁸F]FAPI-42 and [⁶⁸Ga]Ga-FAPI-04 PET/CT were performed in 12 patients to compare biodistribution, tumor uptake, and tumor detection ability. Results [¹⁸F]FAPI-42 uptake in the tumors was rapid and reached a high level with an average SUVmax of 15.8 at 18 min, which stayed at a similarly high level to 2 h. The optimal image acquisition time for [¹⁸F]FAPI-42 was determined to be 1 h postinjection. For tumor detection, [¹⁸F]FAPI-42 had a high uptake and could be clearly visualized in the lesions. Compared to [⁶⁸Ga]Ga-FAPI-04, [¹⁸F]FAPI-42 had the same detectability for 144 positive lesions. In addition, [¹⁸F]FAPI-42 showed a higher SUVmax in liver and bone lesions (P < 0.05) and higher TBRs in liver, bone, lymph node, pleura, and peritoneal lesions (all P < 0.05). Conclusion The present study demonstrates that the optimal image acquisition time of [¹⁸F]FAPI-42 is 1 h postinjection and that [¹⁸F]FAPI-42 exhibits comparable lesion detectability to [⁶⁸Ga]Ga-FAPI-04. Trial registration Chinese Clinical Trial Registry (ChiCTR2100045757).

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