Introduction: the diagnostic performance of [⁶⁴Cu]-DOTAGA-PSMA PET–CT imaging was compared retrospectively to [¹⁸F]-PSMA PET–CT in prostate cancer patients with recurrent disease and in the primary staging of selected patients with advanced local and possible metastatic disease. Methods: We retrospectively selected a total of 100 patients, who were consecutively examined in our department, with biochemical recurrence after radical prostatectomy or who had progressive local and possible metastatic disease in the last 3 months prior to this investigation. All patients were examined with a dedicated PET–CT scanner (Biograph; Siemens Healthineers). A total of 250 MBq (3.5 MBq per kg bodyweight, range 230–290 MBq) of [⁶⁴Cu]-DOTAGA-PSMA or [¹⁸-F]-PSMA was applied intravenously. PET images were performed 1 h post-injection (skull base to mid-thigh). The maximum standardized uptake values (SUVmax) of PSMA-positive lesions and the mean standardized uptake value (SUVmean) of the right liver lobe were measured. Results: All but 9/50 of the patients (18%; PSA range: 0.01–0.7 µg/L) studied with [⁶⁴Cu]-DOTAGA-PSMA and 6/50 of the ones (12%; PSA range: 0.01–4.2) studied with [¹⁸F]-PSMA had at least one positive PSMA lesion shown by PET–CT. The total number of lesions was higher with [⁶⁴Cu]-DOTAGA-PSMA (209 vs. 191); however, the median number of lesions was one for [⁶⁴Cu]-DOTAGA-PSMA and two for [¹⁸F]-PSMA. Interestingly, the median SUVmean of the right liver lobe was slightly higher for [¹⁸F]-PSMA (11.8 vs. 8.9). Conclusions: [⁶⁴Cu]-DOTAGA-PSMA and [¹⁸F]-PSMA have comparable detection rates for the assessment of residual disease in patients with recurrent or primary progressive prostate cancer. The uptake in the liver is moderately different, and therefore at least the SUVs of the lesions in both studies would not be comparable.

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