Head-to-head intra-individual comparison of biodistribution and tumor uptake of ${}^{68}$Ga-FAPI and ${}^{18}$F-FDG PET/CT in cancer patients

FAPI ligands (fibroblast activation protein inhibitor), a novel class of radiotracers for PET/CT imaging, demonstrated in previous studies rapid and high tumor uptake. The purpose of this study is the head-to-head intra-individual comparison of ${}^{68}$Ga-FAPI versus standard-of-care ${}^{18}$F-FDG in PET/CT in organ biodistribution and tumor uptake in patients with various cancers. This international retrospective multicenter analysis included PET/CT data from 71 patients from 6 centers who underwent both ${}^{68}$Ga-FAPI and ${}^{18}$F-FDG PET/CT within a median time interval of 10 days (range 1-89 days). Volumes of interest (VOIs) were manually drawn in normal organs and tumor lesions to quantify tracer uptake by SUVmax and SUVmean. Furthermore, tumor-to-background ratios (TBR) were generated (SUVmax tumor/ SUVmax organ). A total of 71 patients were studied of, which 28 were female and 43 male (median age 60). In 41 of 71 patients, the primary tumor was present. Forty-three of 71 patients exhibited 162 metastatic lesions. ${}^{68}$Ga-FAPI uptake in primary tumors and metastases was comparable to ${}^{18}$F-FDG in most cases. The SUVmax was significantly lower for ${}^{68}$Ga-FAPI than ${}^{18}$F-FDG in background tissues such as the brain, oral mucosa, myocardium, blood pool, liver, pancreas, and colon. Thus, ${}^{68}$Ga-FAPI TBRs were significantly higher than ${}^{18}$F-FDG TBRs in some sites, including liver and bone metastases. Quantitative tumor uptake is comparable between ${}^{68}$Ga-FAPI and ${}^{18}$F-FDG, but lower background uptake in most normal organs results in equal or higher TBRs for ${}^{68}$Ga-FAPI. Thus, ${}^{68}$Ga-FAPI PET/CT may yield improved diagnostic information in various cancers and especially in tumor locations with high physiological ${}^{18}$F-FDG uptake.