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Radiohybrid prostate-specific membrane antigen (rhPSMA) ligands are a new class of prostate cancer theranostic agents. 18 F-rhPSMA-7 offers the advantages of 18 F labeling and low urinary excretion compared with 68 Ga-PSMA-11. Here, we compare the frequency of non-tumor-related uptake and tumor positivity with 68 Ga-PSMA-11 and 18 F-rhPSMA-7 in patients with primary or recurrent prostate cancer. Methods: This retrospective matched-pair comparison matched 160 18 F-rhPSMA-7 with 160 68 Ga-PSMA-11 PET/CT studies for primary staging ( n = 33) and biochemical recurrence ( n = 127) according to clinical characteristics. Two nuclear medicine physicians reviewed all scans, first identifying all PET-positive lesions and then differentiating lesions suggestive of prostate cancer from those that were benign, on the basis of known pitfalls and ancillary information from CT. For each region, the SUV max of the lesion with the highest PSMA ligand uptake was noted. Tumor positivity rates were determined, and SUV max was compared separately for each tracer. Results:  18 F-rhPSMA-7 and 68 Ga-PSMA-11 PET revealed 566 and 289 PSMA ligand-positive lesions, respectively. Of these, 379 and 100 lesions, equaling 67.0% and 34.6%, respectively, of all PSMA-positive lesions, were considered benign. The distribution of their etiology was similar (42%, 24%, and 25% with 18 F-rhPSMA-7 vs. 32%, 24%, and 38% with 68 Ga-PSMA-11 for ganglia, bone, and unspecific lymph nodes, respectively). All primary tumors were positive with both agents ( n = 33 each), whereas slightly more metastatic lesions were observed with 68 Ga-PSMA-11 in both disease stages (113 for 18 F-rhPSMA-7 and 124 for 68 Ga-PSMA-11). The SUV max of 18 F-rhPSMA-7 and 68 Ga-PSMA-11 did not differ ( P &gt; 0.05) in local recurrence or primary prostate cancer; however, the tumor-to-bladder ratio was significantly higher with 18 F-rhPSMA-7 (4.9 ± 5.3 vs. 2.2 ± 3.7, P = 0.02, for local recurrence; 9.8 ± 9.7 vs. 2.3 ± 2.6, P &lt; 0.001, for primary prostate cancer). Conclusion: The tumor positivity rate was consistently high for 68 Ga-PSMA-11 and 18 F-rhPSMA-7. Both tracers revealed a considerable number of areas of uptake that were reliably identified as benign by trained physicians making use of corresponding morphologic imaging and known PSMA pitfalls. These were more frequent with 18 F-rhPSMA-7. However, the matched-pair comparison could have introduced a source of bias. Adequate reader training can allow physicians to differentiate benign uptake from disease and be able to benefit from the logistical and clinical advantages of 18 F-rhPSMA-7.

journal of nuclear medicine

Matched-Pair Comparison of <sup>68</sup>Ga-PSMA-11 and <sup>18</sup>F-rhPSMA-7 PET/CT in Patients with Primary and Biochemical Recurrence of Prostate Cancer: Frequency of Non–Tumor-Related Uptake and Tumor Positivity

Matched-Pair Comparison of 68Ga-PSMA-11 and 18F-rhPSMA-7 PET/CT in Patients with Primary and Biochemical Recurrence of Prostate Cancer: Frequency of Non–Tumor-Related Uptake and Tumor Positivity

Matched-Pair Comparison of ⁶⁸Ga-PSMA-11 and ¹⁸F-rhPSMA-7 PET/CT in Patients with Primary and Biochemical Recurrence of Prostate Cancer: Frequency of Non–Tumor-Related Uptake and Tumor Positivity