Abstract Background Liver uptake in [⁶⁸Ga]Ga-PSMA-11 PET is used as an internal reference in addition to clinical parameters to select patients for [¹⁷⁷Lu]Lu-PSMA-617 radioligand therapy (RLT). Due to increased demand, [⁶⁸Ga]Ga-PSMA-11 was replaced by [¹⁸F]F-PSMA-1007, a more lipophilic tracer with different biodistribution and splenic uptake was suggested as a new internal reference. We compared the intra-patient tracer distribution between [⁶⁸Ga]Ga-PSMA-11 and [¹⁸F]F-PSMA-1007. Methods Fifty patients who underwent PET examinations in two centers with both [¹⁸F]F-PSMA-1007 and [⁶⁸Ga]Ga-PSMA-11 within one year were included. Mean standardized uptake values (SUV_mean) were obtained for liver, spleen, salivary glands, blood pool, and bone. Primary tumor, local recurrence, lymph node, bone or visceral metastasis were also assessed for intra- and inter-individual comparison. Results Liver SUV_mean was significantly higher with [¹⁸F]F-PSMA-1007 (11.7 ± 3.9) compared to [⁶⁸Ga]Ga-PSMA-11 (5.4 ± 1.7, p < .05) as well as splenic SUV_mean (11.2 ± 3.5 vs.8.1 ± 3.5, p < .05). The blood pool was comparable between the two scans. Malignant lesions did not show higher SUV_mean on [¹⁸F]F-PSMA-1007. Intra-individual comparison of liver uptake between the two scans showed a linear association for liver uptake with SUV_mean [⁶⁸Ga]Ga-PSMA-11 = 0.33 x SUV_mean [¹⁸F]F-PSMA-1007 + 1.52 (r = .78, p < .001). Conclusion Comparing biodistribution of [⁶⁸Ga]Ga and [¹⁸F]F tracers, liver uptake on [⁶⁸Ga]Ga-PSMA-11 PET is the most robust internal reference value. Liver uptake of [¹⁸F]F-PSMA-1007 was significantly higher, but so was the splenic uptake. The strong intra-individual association of hepatic accumulation between the two scans may allow using of a conversion factor for [¹⁸F]F-PSMA-1007 as a basis for RLT selection.