¹⁸F-labeled prostate-specific membrane antigen (PSMA)-ligand PET has several principal advantages over ⁶⁸Ga-PSMA-11. The purpose of this retrospective study was to evaluate the frequency of non-tumor-related uptake and the detection efficacy comparing ⁶⁸Ga-PSMA-11 PET/CT and ¹⁸F-PSMA-1007 PET/CT in recurrent prostate cancer (PC) patients. Methods: The study included 102 patients with biochemically recurrent PC after radical prostatectomy undergoing ¹⁸F-PSMA-1007 PET/CT imaging. On the basis of various clinical variables, patients with corresponding ⁶⁸Ga-PSMA-11 PET/CT scans were matched. All PET/CT scans (n = 204) were reviewed by 1 nuclear medicine physician. First, all PET-positive lesions were noted. Then, lesions suspected of being recurrent PC were differentiated from lesions attributed to a benign origin on the basis of known pitfalls and information from CT. For each region, the SUV_max of the lesion with the highest PSMA-ligand uptake was noted. Detection rates were determined, and SUV_max was compared separately for ⁶⁸Ga-PSMA-11 and ¹⁸F-PSMA-1007. Results: In total, ¹⁸F-PSMA-1007 PET and ⁶⁸Ga-PSMA-11 PET revealed 369 and 178 PSMA-ligand-positive lesions, respectively. ¹⁸F-PSMA-1007 PET revealed approximately 5 times more lesions attributed to a benign origin than did ⁶⁸Ga-PSMA-11 PET (245 vs. 52 lesions, respectively). The benign lesions most frequently observed were ganglia, unspecific lymph node, and bone lesions, at a rate of 43%, 31%, and 24% for ¹⁸F-PSMA-1007 PET and 29%, 42%, and 27% for ⁶⁸Ga-PSMA-11 PET, respectively. The SUV_max of lesions attributed to a benign origin was significantly higher (P < 0.0001) for ¹⁸F-PSMA-1007 PET. Further, a similar number of lesions was attributed to recurrent PC (124/369 for ¹⁸F-PSMA-1007 PET and 126/178 for ⁶⁸Ga-PSMA-11 PET). Conclusion: The number of lesions with increased PSMA-ligand uptake attributed to a benign origin is considerably higher for ¹⁸F-PSMA-1007 PET than for ⁶⁸Ga-PSMA-11 PET. This finding indicates the need for sophisticated reader training emphasizing known pitfalls and reporting within the clinical context.

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