PURPOSE: PSMA-PET is a reference standard examination for patients with prostate cancer, but even using recently introduced digital PET detectors image acquisition with standard field-of-view scanners is still in the range of 20 min. This may cause limited access to examination slots because of the growing demand for PSMA-PET. Ultra-fast PSMA-PET may enhance throughput but comes at the cost of poor image quality. The aim of this manuscript is to evaluate the accuracy of AI-enhanced ultra-fast PSMA-PET for staging of patients with prostate cancer. METHODS: A total number of 357 whole-body [ RESULTS: The AI-network significantly improved the visual image quality and detection rate in most miTNM regions compared with the non-enhanced image data (T: 69.6% vs. 43.5%, p <
0.05
N: 46.3% vs. 27.8%, p <
0.01
M1a 64.4% vs. 47.5%, p <
0.01
M1b: 85.7% vs. 72.1%, p <
0.01). However, improvement was not significant for the M1c category (42.9 vs. 28.6%, p >
0.05). Missed lesions had a smaller SUVmax and lesion size compared with detected lesions (exemplary for N: 9.5 vs. 26.5 SUVmax
4 vs. 10 mm). SUVmax values of lesions were significantly different in all miTNM regions between the ultra-fast and reference standard PET, but only in the T-region between the AI-enhanced and reference standard PET. CONCLUSION: The AI-based image enhancement improved image quality and region detection rates by a mean of 17.9%. As the sensitivity of synthetic PET for small and low-uptake lesions was limited, a potential clinical use case could be disease monitoring in patients with high tumor volume and PSMA uptake undergoing PSMA radioligand therapy. The improvement in detection rate of distant metastases was not significant. This indicates that more training data is needed to ensure robust results also for lesions that have lower appearance frequency. Future studies on accelerated PSMA-PET seem warranted.