Expanding the role of small-molecule PSMA ligands beyond PET staging of prostate cancer

Prostate-specific membrane antigen (PSMA) positron emission tomography (PET) is rapidly being established as arguably the leading contemporary imaging modality in the management of prostate cancer. Outside of its conventional use in the de novo staging of localized disease and detection of biochemical recurrence, additional applications for the use of PSMA PET are emerging. Uptake of PSMA tracers in other genitourinary malignancies, particularly renal cell carcinoma, has led to new fields of investigation. Therapeutic delivery of radiolabelled PSMA small molecules has shown considerable promise in advanced prostate cancer. The ability to use the same molecule for imaging and therapy — theranostics — enables a highly personalized approach. PSMA PET can also have a considerable influence in the selection and guidance of radiotherapy fields for high-risk and recurrent disease. Intriguingly, changes in intensity of PSMA uptake during systemic therapy might provide early response assessment or novel insight into the biological responses of genitourinary malignancies to treatment. An evolving range of radiolabelled PSMA radiopharmaceuticals is emerging in the multiple facets of modern clinical practice. In this Review, Siva and colleagues discuss the uses of (PSMA)–positron emission tomography (PET) beyond its role in conventional prostate cancer imaging. PSMA could have utility in other genitourinary malignancies and oligometastatic prostate cancer, theranostics, selection and guidance of radiotherapy fields, as well as the assessment of response to treatment.