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 177Lu 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.

中文翻译：

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为什么针对PSMA的目标是改变前列腺癌管理的游戏规则。

前列腺特异性膜抗原（PSMA）是一种在前列腺腺癌中高表达的跨膜糖蛋白，在良性和前列腺外组织中仅表现出有限的表达，因此代表了诊断和管理前列腺癌的理想靶标。自30年前被发现以来，为开发针对PSMA的临床技术做出了巨大的努力。在过去的5年中，针对PSMA的用于诊断和治疗用途的新型药物的开发出现了爆炸式增长。已经针对SPECT和PET平台开发了针对PSMA的成像剂。在高风险的局部疾病状态，治疗后生化复发的患者以及晚期疾病中，PSMA PET成像似乎优于传统成像。迄今为止，大多数关于治疗剂的临床研究报告都使用了靶向PSMA的放射性金属，将β射线传递到转移性疾病部位，其中177Lu是研究最广泛的治疗性放射性同位素。抗体和小分子试剂的研究已经发表，并显示出令人鼓舞的结果。由于唾液腺中小分子药物的吸收，安全性似乎一般仅限于轻度的短暂性骨髓毒性和口干症。放射学反应可能是剧烈的，并且观察到疼痛减轻。然而，对总体生存的影响尚待证实。抗体和小分子试剂的研究已经发表，并显示出令人鼓舞的结果。由于唾液腺中摄取了小分子药物，因此安全性似乎通常仅限于轻度的短暂性骨髓毒性和口干症。放射学反应可能是剧烈的，并且观察到疼痛减轻。然而，对总体生存的影响尚待证实。抗体和小分子试剂的研究已经发表，并显示出令人鼓舞的结果。由于唾液腺中小分子药物的吸收，安全性似乎一般仅限于轻度的短暂性骨髓毒性和口干症。放射学反应可能是剧烈的，并且观察到疼痛减轻。然而，对总体生存的影响尚待证实。