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Why Targeting PSMA Is a Game Changer in the Management of Prostate Cancer.

Prostate-specific membrane antigen (PSMA) is a transmembrane glycoprotein that is highly expressed on prostate adenocarcinomas, exhibits only limited expression in benign and extraprostatic tissues, and thus represents an ideal target for the diagnosis and management of prostate cancer. Since its discovery over 30 y ago, significant effort has been made to develop clinical technology targeting PSMA. The last 5 y have seen an explosion of development of new agents targeting PSMA for diagnostic and therapeutic use. Imaging agents targeting PSMA have been developed for SPECT and PET platforms. PSMA PET imaging appears to outperform traditional imaging in the high-risk localized-disease state, in patients with biochemical recurrence after treatment, and in advanced disease. To date, most of the reported clinical studies of therapeutic agents have used PSMA-targeted radiometals to deliver β-radiation to metastatic disease sites, with 177 Lu being the most widely investigated therapeutic radioisotope. Studies of both antibodies and small-molecule agents have been published and have demonstrated encouraging results. Safety appears generally limited to mild transient bone marrow toxicity and xerostomia because of uptake of the small-molecule agents in the salivary glands. Radiologic responses can be dramatic, and decreases in pain have been observed. The effect on overall survival, however, has yet to be demonstrated.

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