Matched-pair comparison of 68Ga-PSMA-11 and 18F-rhPSMA-7 PET/CT in patients with primary and biochemical recurrent prostate cancer

42 Purpose: 18F-labeled prostate-specific membrane antigen (PSMA)-ligand positron emission tomography/computed tomography (PET/CT) is increasingly used for prostate cancer imaging due to several major principal advantages (image contrast/noise, logistics, positron range) compared to 68Ga-PSMA-11. We aimed to evaluate frequency of non-tumor related uptake and tumor positivity comparing 68Ga-PSMA-11and the recently introduced 18F-rhPSMA-7 (providing low urinary excretion) in patients with both primary and recurrent prostate cancer (PC). Methods and Materials: This retrospective matched-pair comparison included 160 18F-rhPSMA-7PET/CT and 160 68Ga-PSMA-11PET/CT studies both for primary staging (n=33) and biochemical recurrence (n=127) matched by various clinical variables. All PET/CTs were reviewed by two nuclear medicine physicians in consensus. First, all PET positive lesions, defined as focal uptake above surrounding background and not physiological distribution, were identified. Then, lesions suspicious for PC were differentiated from lesions attributed to benign origin based on known pitfalls and information from CT. For each region, SUVmax of the lesion with the highest PSMA-ligand uptake was noted. Tumor positivity rates were determined and SUVmax were compared separately for 68Ga-PSMA-11 and 18F-rhPSMA-7. Results: In total, 18F-rhPSMA-7PET and 68Ga-PSMA-11 revealed 532 and 293 PSMA-ligand positive lesions, respectively. The absolute number of lesions attributed to benign origin was 3.3 times higher for 18F-rhPSMA-7PET compared to 68Ga-PSMA-11 PET (351 vs. 105 lesions, respectively), whilst the distribution of their etiology was relatively similar (46%, 27%, 20% in 18F-rhPSMA-7vs. 30%, 40%, 20% in 68Ga-PSMA-11 for ganglia, unspecific LN and bone lesions, respectively). All primary tumors were positive in 18F-rhPSMA-7 and68Ga-PSMA-11 (n=33 each) while a slightly higher number of metastatic lesions was observed with 68Ga-PSMA-11 in primary staging (16 for 18F-rhPSMA-7 and 21 for 68Ga-PSMA-11). In biochemical recurrence a similar number of malignant lesions (132 for 18F-rhPSMA-7 and 134 for 68Ga-PSMA-11) were detected. SUVmax of all malignant lesions was significantly higher (p<0.01) in 18F-rhPSMA-7 PET (SUVmax 26.7±28.8 for 18F-rhPSMA-7 PET and 17.9±18.7 for 68Ga-PSMA-11 PET, respectively) while SUVmax of the urinary bladder was significantly lower in 18F-rhPSMA-7 PET (SUVmax 3.8±1.9 for 18F-rhPSMA-7 PET and 11.2±14.0 for 68Ga-PSMA-11 PET, respectively). Current limitations include the lack of histopathological proof of detected lesions. Conclusions: While tumor positivity rate is consistently high for 18F-rhPSMA-7, a considerably higher number of lesions with increased PSMA-ligand uptake attributed to benign lesions is present compared to 68Ga-PSMA-11. However, after adequate reader training, physicians should be well equipped to distinguish likely malignant lesions from those that are most probably benign, while fully exploiting the logistical advantages of 18F-labeled PSMA-ligands.