Prostate-specific membrane antigen (PSMA) as a transmembrane protein is overexpressed by prostate cancer (PC) cells and is accessible for binding antibodies or low-molecular-weight radioligands due to its extracellular portion. Successful targeting of PSMA began with the development of humanized J591 antibody. Due to their faster clearance compared to antibodies, small-molecule radioligands for targeted imaging and therapy of PC have been favored in recent development efforts. PSMA positron emission tomography (PET) imaging has higher diagnostic performance than conventional imaging for initial staging of high-risk PC and biochemical recurrence detection/localization. However, it remains to be demonstrated how to integrate PSMA PET imaging for therapy response assessment and as an outcome endpoint measure in clinical trials. With the recent approval of 177Lu-PSMA-617 by the US Food and Drug Administration for metastatic castration-resistant PC progressing after chemotherapy, the high value of PSMA-targeted therapy was confirmed. Compared to standard of care, PSMA-based radioligand therapy led to a better outcome and a higher quality of life. This review, focusing on the advanced PC setting, provides an overview of different approved and nonapproved PSMA-targeted imaging and therapeutic modalities and discusses the future of PSMA-targeted theranostics, also with an outlook on non-radiopharmaceutical-based PSMA-targeted therapies.

中文翻译：

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前列腺特异性膜抗原：治疗晚期前列腺癌的途径

前列腺特异性膜抗原 (PSMA) 作为一种跨膜蛋白，在前列腺癌 (PC) 细胞中过度表达，并且由于其细胞外部分而易于结合抗体或低分子量放射性配体。 PSMA 的成功靶向始于人源化 J591 抗体的开发。由于与抗体相比清除速度更快，用于 PC 靶向成像和治疗的小分子放射性配体在最近的开发工作中受到青睐。 PSMA 正电子发射断层扫描 (PET) 成像比传统成像具有更高的诊断性能，可用于高风险 PC 的初始分期和生化复发检测/定位。然而，如何整合 PSMA PET 成像来评估治疗反应并作为临床试验中的结果终点指标仍有待证明。随着最近的批准177Lu-PSMA-617被美国食品和药物管理局针对化疗后进展的转移性去势抵抗PC，证实了PSMA靶向治疗的高价值。与标准护理相比，基于 PSMA 的放射配体治疗可带来更好的结果和更高的生活质量。这篇综述重点关注先进的 PC 设置，概述了不同的已批准和未批准的 PSMA 靶向成像和治疗方式，并讨论了 PSMA 靶向治疗诊断的未来，并对基于非放射性药物的 PSMA 靶向治疗进行了展望。