靶向胃蛋白释放肽受体的放射药物用于诊断和治疗前列腺癌
Radiopharmaceuticals Targeting Gastrin-Releasing Peptide Receptor for Diagnosis and Therapy of Prostate Cancer
影响因子:4.50000
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
摘要
前列腺癌（PC）的高发病率和重型疾病负担需要准确而全面的评估，以进行适当的疾病管理。前列腺特异性膜抗原（PSMA）正电子发射断层扫描（PET）仍无法检测到PSMA阴性病变，尽管其在PC疾病管理中的关键作用。据报道，PC病变中胃蛋白释放肽受体（GRPR）的过表达是PC诊断和治疗的补充靶标。已经开发了源自GRPR天然配体的放射性药物。这些放射性药物可以实现人体内GRPR的可视化和定量，可用于疾病评估和治疗指导。最近开发的放射性药物表现出改善的药代动力学参数，而没有亲和力恶化。靶向GRPR的几种异二聚体已被构造为替代方法，因为它们有潜力检测单个靶标检测的诊断效率低的肿瘤病变。此外，一些靶向GRPR的放射性药物已经进入了临床试验，用于对PC进行初始分期或生化复发检测以指导疾病分层和治疗，这表明PC疾病管理中的潜力很大。本文中，我们全面总结了针对GRPR的放射性药物的进展。特别是，我们讨论了配体，螯合剂和接头对放射性药物分布的影响。此外，我们总结了一种潜在的设计方案，以促进放射性药物的发展，从而迅速临床翻译。
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.