Review

靶向胃泌素释放肽受体的放射性药物在前列腺癌诊断与治疗中的应用

Radiopharmaceuticals Targeting Gastrin-Releasing Peptide Receptor for Diagnosis and Therapy of Prostate Cancer

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MOLECULAR PHARMACEUTICS

影响因子:4.5

分区:医学2区 / 药学2区医学：研究与实验3区

发表日期:2024 Sep 02

作者: Yuheng Zou, Mingxing Huang, Mingxing Hu, Hui Wang, Wei Chen, Rong Tian

DOI: 10.1021/acs.molpharmaceut.4c00066

摘要

前列腺癌（PC）具有高发率和沉重的疾病负担，需进行精准全面的评估以实现适当的疾病管理。尽管前列腺特异性膜抗原（PSMA）正电子发射断层扫描（PET）在前列腺癌的疾病管理中起关键作用，但无法检测PSMA阴性病变。报道显示，胃泌素释放肽受体（GRPR）在前列腺癌病变中的过表达，可作为诊断和治疗的互补靶点。基于GRPR天然配体开发的放射性药物已被研制出来。这些药物使得体内GRPR的可视化和定量成为可能，可用于疾病评估和治疗指导。近期开发的放射性药物显示出改善的药代动力学参数，而亲和力未受影响。为了检测肿瘤病灶，一些靶向GRPR的异二聚体也被构建，作为单一靶点检测诊断效率低的替代品。此外，一些靶向GRPR的放射性药物已进入临床试验，用于前列腺癌的初期分期或生化复发检测，以指导疾病分层和治疗，显示出在前列腺癌疾病管理中的巨大潜力。本文全面总结了靶向GRPR的放射性药物的研究进展，特别讨论了配体、螯合剂和连接体对药物分布的影响，并总结了促进药物开发和临床转化的潜在设计方案。

Abstract

The high incidence and heavy disease burden of prostate cancer (PC) require accurate and comprehensive assessment for appropriate disease management. Prostate-specific membrane antigen (PSMA) positron emission tomography (PET) cannot detect PSMA-negative lesions, despite its key role in PC disease management. The overexpression of gastrin-releasing peptide receptor (GRPR) in PC lesions reportedly performs as a complementary target for the diagnosis and therapy of PC. Radiopharmaceuticals derived from the natural ligands of GRPR have been developed. These radiopharmaceuticals enable the visualization and quantification of GRPR within the body, which can be used for disease assessment and therapeutic guidance. Recently developed radiopharmaceuticals exhibit improved pharmacokinetic parameters without deterioration in affinity. Several heterodimers targeting GRPR have been constructed as alternatives because of their potential to detect tumor lesions with a low diagnostic efficiency of single target detection. Moreover, some GRPR-targeted radiopharmaceuticals have entered clinical trials for the initial staging or biochemical recurrence detection of PC to guide disease stratification and therapy, indicating considerable potential in PC disease management. Herein, we comprehensively summarize the progress of radiopharmaceuticals targeting GRPR. In particular, we discuss the impact of ligands, chelators, and linkers on the distribution of radiopharmaceuticals. Furthermore, we summarize a potential design scheme to facilitate the advancement of radiopharmaceuticals and, thus, prompt clinical translation.