Department of Urology, David Geffen School of Medicine at UCLA, Los Angeles, California
Department of Urology, David Geffen School of Medicine at UCLA, Los Angeles, California.
J Nucl Med. 2018 Feb;59(2):177-182. doi: 10.2967/jnumed.117.191874. Epub 2017 Oct 6.
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 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.
前列腺特异性膜抗原（PSMA）是一种跨膜糖蛋白，在前列腺腺癌中高度表达，在良性和前列腺外组织中仅有限表达，因此是诊断和治疗前列腺癌的理想靶点。自 30 多年前发现以来，人们已经做出了巨大的努力来开发针对 PSMA 的临床技术。在过去的 5 年中，针对 PSMA 的新型诊断和治疗用靶向药物得到了迅速发展。已经开发了用于 SPECT 和 PET 平台的针对 PSMA 的成像剂。PSMA PET 成像似乎在高危局限性疾病状态、治疗后生化复发的患者以及晚期疾病中优于传统成像。迄今为止，大多数报告的治疗剂的临床研究都使用 PSMA 靶向放射性金属将β射线递送至转移性疾病部位，Lu 是研究最多的治疗放射性同位素。已经发表了针对抗体和小分子药物的研究，并取得了令人鼓舞的结果。由于小分子药物在唾液腺中的摄取，安全性通常仅限于轻度短暂的骨髓毒性和口干。放射学反应可能非常显著，并且观察到疼痛减轻。然而，尚未证明对总生存的影响。
