Department of Nuclear Medicine, University Medical Center Freiburg, Faculty of Medicine, University of Freiburg, Hugstetter Str. 55, 79106, Freiburg, Germany.
Division of Radiopharmaceutical Development, German Cancer Consortium (DKTK), Partner Site Freiburg, Freiburg, Germany and German Cancer Research Center, Heidelberg, Germany.
Curr Oncol Rep. 2023 Nov;25(11):1363-1374. doi: 10.1007/s11912-023-01458-6. Epub 2023 Oct 20.
[Lu]Lu-PSMA-617 is a radiopharmaceutical that emits beta-minus radiation and targets prostate-specific membrane antigen (PSMA)-positive prostate cancer. Despite its clinical success, there are still patients not showing sufficient response rates. This review compiles latest studies aiming at therapy improvement in [Lu]Lu-PSMA-617-naïve and -resistant patients by alternative or combination treatments.
A variety of agents to combine with [Lu]Lu-PSMA-617 are currently under investigation including alpha radiation-emitting pharmaceuticals, radiosensitizers, taxane chemotherapeutics, androgen receptor pathway inhibitors, immune checkpoint inhibitors, and external beam radiation. Actinium-225 (Ac)-labeled PSMA-targeting inhibitors are the most studied pharmaceuticals for combination therapy or as an alternative for treatment after progression under [Lu]Lu-PSMA-617 therapy. Alpha emitters seem to have a potential of achieving a response to PSMA-targeting radionuclide therapy in both initial non-responders or responders to [Lu]Lu-PSMA-617 later developing treatment resistance. Emerging evidence for immunostimulatory effects of radiopharmaceuticals and first prospective studies support the combination of [Lu]Lu-PSMA-617 and immune checkpoint inhibition for late-stage prostate cancer.
[Lu]Lu-PSMA-617 是一种发射β-射线的放射性药物，靶向前列腺特异性膜抗原（PSMA）阳性前列腺癌。尽管其临床应用取得了成功，但仍有部分患者的反应率不够高。本综述汇集了最新的研究，旨在通过替代或联合治疗改善[Lu]Lu-PSMA-617 初治和耐药患者的治疗效果。
目前正在研究多种与[Lu]Lu-PSMA-617 联合使用的药物，包括发射α射线的药物、放射增敏剂、紫杉烷类化疗药物、雄激素受体通路抑制剂、免疫检查点抑制剂和外照射放疗。钍-225（Ac）标记的 PSMA 靶向抑制剂是联合治疗或在[Lu]Lu-PSMA-617 治疗后进展时作为替代治疗的最有研究前景的药物。α发射体似乎有潜力使 PSMA 靶向放射性核素治疗在初始无反应者或对[Lu]Lu-PSMA-617 有反应但后来出现治疗耐药的患者中获得反应。放射性药物的免疫刺激作用的新证据和首批前瞻性研究支持将[Lu]Lu-PSMA-617 与免疫检查点抑制联合用于晚期前列腺癌的治疗。
