Purpose: Radiohybrid prostate-specific membrane antigen (rhPSMA) ligands are a new class of ¹⁸F-labeled PSMA-targeting agents. ¹⁸F-rhPSMA-7.3 is a lead compound which is currently under investigation in two multicenter phase III trials for PET-imaging. Here, we report the first retrospective data on its detection efficacy and potential impact on clinical management in a homogeneous cohort of patients with biochemical recurrence after radical prostatectomy, and prior to any salvage therapy. Methods: 242 patients (median [range] PSA, 0.60 [0.2-60.8] ng/mL) who underwent ¹⁸F-rhPSMA-7.3 PET/CT were retrospectively selected from the institutions' database. Images were re-read by an experienced nuclear medicine physician. Lesion detection rates were stratified by PSA. Further, potential management before and after PET was assessed by an interdisciplinary simulated tumor board and categorized (major vs. minor vs. no therapeutic change). The distribution of management change identified in each PSA subgroup was determined. Results: In total, 176/242 (72.7%) patients showed PSMA-ligand positive findings. ¹⁸F-rhPSMA-7.3 detection rates were 61.8% (63/102), 67.9% (38/56), 81.1% (30/37) and 95.7% (45/47) for PSA-levels of 0.2-<0.5 ng/mL, 0.5-<1 ng/mL, 1-<2 ng/mL and ≥2 ng/mL, respectively. ¹⁸F-rhPSMA-7.3 PET/CT revealed local recurrence, pelvic lymph node metastases, retroperitoneal lymph nodes metastases, supradiaphragmatic lymph nodes, bone metastases, and visceral metastases in 48.8% (n = 118), 28.9% (n = 70), 6.6% (n = 16), 1.2% (n = 3), 13.2% (n = 32) and 1.2% (n = 3) of patients, respectively. Notably, bone lesions were identified in 8.8% of patients (9/102) with PSA <0.5 ng/mL. Results from the interdisciplinary simulated tumor board indicated change of therapeutic management in 153/242 patients (63.2%) with 54/242 (22.3%) considered major and 99/242 (40.9%) minor, respectively. ¹⁸F-rhPSMA-7.3 PET/CT did not prompt any therapeutic changes in 64/242 patients (26.4%). Conclusion: ¹⁸F-rhPSMA-7.3 PET offers high detection efficacy in patients with biochemical recurrence after radical prostatectomy, and prior to potential salvage therapy, and results in a potential change in treatment plans in nearly 2/3 of patients. Keywords: Biochemical recurrence; hybrid imaging; positron emission tomography; prostate cancer; prostate-specific membrane antigen.

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