Department of Radiology, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA.
Department of Radiation Oncology, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA.
Int J Mol Sci. 2022 Jan 21;23(3):1158. doi: 10.3390/ijms23031158.
In the past two decades, extensive efforts have been made to develop agents targeting prostate-specific membrane antigen (PSMA) for prostate cancer imaging and therapy. To date, represented by two recent approvals of [Ga]Ga-PSMA-11 and [F]F-DCFPyL by the United States Food and Drug Administration (US-FDA) for positron emission tomography (PET) imaging to identify suspected metastases or recurrence in patients with prostate cancer, PSMA-targeting imaging and theranostic agents derived from small molecule PSMA inhibitors have advanced to clinical practice and trials of prostate cancer. The focus of current development of new PSMA-targeting agents has thus shifted to the improvement of in vivo pharmacokinetics and higher specific binding affinity with the aims to further increase the detection sensitivity and specificity and minimize the toxicity to non-target tissues, particularly the kidneys. The main strategies involve systematic chemical modifications of the linkage between the targeting moiety and imaging/therapy payloads. In addition to a summary of the development history of PSMA-targeting agents, this review provides an overview of current advances and future promise of PSMA-targeted imaging and theranostics with focuses on the structural determinants of the chemical modification towards the next generation of PSMA-targeting agents.
在过去的二十年中，人们做出了广泛的努力来开发针对前列腺特异性膜抗原（PSMA）的药物，用于前列腺癌的成像和治疗。迄今为止，美国食品和药物管理局（US-FDA）最近批准了两种[Ga]Ga-PSMA-11 和 [F]F-DCFPyL 用于正电子发射断层扫描（PET）成像，以识别前列腺癌患者疑似转移或复发，基于小分子 PSMA 抑制剂的 PSMA 靶向成像和治疗药物已进入临床实践和前列腺癌试验。因此，新型 PSMA 靶向药物的研发重点已转向改善体内药代动力学和更高的与靶标结合特异性，旨在进一步提高检测的灵敏度和特异性，并最大程度地降低对非靶组织（尤其是肾脏）的毒性。主要策略包括靶向部分与成像/治疗有效载荷之间连接的系统化学修饰。除了对 PSMA 靶向药物的发展历史进行总结外，本综述还概述了 PSMA 靶向成像和治疗的最新进展和未来前景，重点介绍了下一代 PSMA 靶向药物的化学修饰的结构决定因素。
