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Prostate-specific membrane antigen (PSMA) is highly expressed on most prostate cancer (PCa) cells, and several PSMA ligands for PET imaging are now available worldwide. 68 Ga-PSMA-11 has already received U.S. Food and Drug Administration and European Medicines Agency approval, and use of PSMA PET is currently suggested by several international guidelines for investigating PCa in different clinical settings. In primary PCa, PSMA PET has been shown to be superior to cross-sectional imaging for the detection of pelvic lymph nodes and distant metastases with subsequent clinical management changes. Additionally, it might also have a role in intraprostatic tumor localization, especially when combined with multiparametric MRI. In a setting of PCa recurrence, higher detection rates have been observed than for any other available imaging techniques, especially at low prostate-specific antigen values. Furthermore, PSMA PET consistently led to a shift in clinical management, thus increasing the proportion of radiotherapy, surgery, or other focal therapies at the expense of systemic options or no treatment. In oligometastatic disease after radical surgery, PSMA PET may be relevant in guiding a metastasis-directed therapy approach, as preliminary data seem to suggest a benefit in terms of progression-free survival after treatment of PSMA PET-positive lesions. As a staging and gatekeeping technique, PSMA PET represents a reliable whole-body imaging procedure in combination with second-line therapy of castration-resistant PCa, as well as being pivotal when assessing patients eligible for radioligand therapy such as 177 Lu-PSMA. This critical review aims at providing a comprehensive overview of the latest literature on the current or emerging main indications, as well as a general outlook on the recommended interpretation criteria for PSMA PET imaging.

Current and Emerging Clinical Applications of PSMA PET Diagnostic Imaging for Prostate Cancer