研究动态
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靶向胃泌素释放肽受体的放射性药物用于前列腺癌的诊断和治疗。

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

发表日期:2024 Sep 02
作者: Yuheng Zou, Mingxing Huang, Mingxing Hu, Hui Wang, Wei Chen, Rong Tian
来源: MOLECULAR PHARMACEUTICS

摘要:

前列腺癌(PC)的高发病率和沉重的疾病负担需要准确和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) 无法检测 PSMA 阴性病变,尽管它在 PC 疾病管理中发挥着关键作用。据报道,PC 病变中胃泌素释放肽受体 (GRPR) 的过度表达可作为 PC 诊断和治疗的补充靶点。源自 GRPR 天然配体的放射性药物已被开发出来。这些放射性药物能够实现体内 GRPR 的可视化和量化,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,且亲和力没有恶化。几种靶向 GRPR 的异二聚体已被构建作为替代方案,因为它们具有检测肿瘤病变的潜力,但单靶标检测的诊断效率较低。此外,一些GRPR靶向放射性药物已进入临床试验,用于PC的初始分期或生化复发检测,以指导疾病分层和治疗,表明在PC疾病管理方面具有巨大潜力。在此,我们全面总结了针对GRPR的放射性药物的进展。我们特别讨论了配体、螯合剂和连接体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进步,从而促进临床转化。
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.