68Ga-FAPI-PET/CT in extra-cervical CUP: Head-to-Head Comparison of 68Ga-FAPI-46 with 18F-FDG in 13 patients.

Abstract Purpose Oncological treatment in a substantial portion of patients with cancer of unknown primary (CUP) remains challenging due to limitations of conventional imaging and positron emission tomography/computed tomography with 18 Fluor-fluorodeoxyglucose ( 18 F-FDG-PET/CT). In head and neck-like CUP (HNCUP), several studies found significantly higher tracer-uptake and detection rates of primary tumors in 68 Gallium-labeled fibroblast activation protein inhibitor-PET/CT ( 68 Ga-FAPI-PET/CT). Here, we address a gap in CUP literature by retrospectively evaluating the diagnostic accuracy of both tracer in a head-to-head comparison of patients with single-site and oligometastatic extra-cervical CUP. Methods 13 patients with extra-cervical CUP underwent both 18 F-FDG- and 68 Ga-FAPI-PET/CT. Suspicious PET-positive lesions were delineated using the volume of interest-technique (50%-isocontour) followed by analysis of maximum and mean standardized uptake values (SUVmax/mean), target-to-background ratios (TBRmax/mean) and tumor-to-tissue ratios (TTRmax/mean). Descriptive analysis was performed and log-transformation was applied to meet model assumptions and stabilize variance. The difference between log-transformed 68 Ga-FAPI- and 18 F-FDG-uptake values was used as outcome variables. Results 21 metastases of 3 patients with single-site and 6 patients with oligometastasized CUP were analyzed. 4 patients with previously extirpated metastases showed no uptake. No increased detection rate of primary tumors could be observed by either tracer. Differences of TBRmax in all metastatic sites and of TTRmax in organ metastases were significant. 68 Ga-FAPI-PET/CT lead to detection of 5/21 additional metastases which were not clearly distinguishable in 18 F-FDG-PET/CT. Conclusion Due to higher tissue contrast in organs, our findings suggest that 68 Ga-FAPI-PET/CT appears favourable compared to 18 F-FDG-PET/CT particularly in patients with suspected distant metastases other than lymph nodes.