Validation of ¹⁸F-rhPSMA-7 and ¹⁸F-rhPSMA-7.3 PET Imaging Results with Histopathology from Salvage Surgery in Patients with Biochemical Recurrence of Prostate Cancer

¹⁸F-rhPSMA-7, and its single diastereoisomer form, ¹⁸F-rhPSMA-7.3, are prostate-specific membrane antigen (PSMA)–targeting radiopharmaceuticals. Here, we investigated their accuracy for the assessment of lymph node (LN) metastases validated by histopathology. Methods: Data from 58 patients with biochemical recurrence of prostate cancer after radical prostatectomy receiving salvage surgery after PET imaging with ¹⁸F-rhPSMA-7 or ¹⁸F-rhPSMA-7.3 were retrospectively reviewed. Two nuclear medicine physicians reviewed all PET scans and morphologic imaging in consensus. Readers were masked from the results of histopathology. PET and morphologic imaging were correlated with histopathology from resected LNs. Results: In 75 of 150 resected regions in 54 of 58 patients, tumor lesions were present in histopathology. The template-based specificity of PET (¹⁸F-rhPSMA-7 and ¹⁸F-rhPSMA-7.3 combined) and morphologic imaging was 93.3% and 100%, respectively. However, ¹⁸F-rhPSMA-7 and ¹⁸F-rhPSMA-7.3 PET detected metastases in 61 of 75 histopathologically proven metastatic LN fields (81.3%) whereas morphologic imaging was positive in only 9 of 75 (12.0%). The positive predictive value was 92.4% for ¹⁸F-rhPSMA-7 and ¹⁸F-rhPSMA-7.3 PET and 100% for morphologic imaging. ¹⁸F-rhPSMA-7 and ¹⁸F-rhPSMA-7.3 PET performance was significantly superior to morphologic imaging (difference in the areas under the receiver-operating-characteristic curves, 0.222; 95% CI, 0.147–0.298; P < 0.001). The mean size of PET-positive and histologically confirmed LN metastases was 6.3 ± 3.1 mm (range, 2–15 mm) compared with a mean size of 9.8 ± 2.5 mm (range, 7–15 mm) on morphologic imaging. Conclusion: ¹⁸F-rhPSMA-7 and ¹⁸F-rhPSMA-7.3 PET offer a high positive predictive value comparable to that reported for ⁶⁸Ga-PSMA-11 and represent a valuable tool for guiding salvage lymphadenectomy.