领航 PD-1/PD-L1 成像示踪剂:从挑战到机遇

Melinda Badenhorst, A. Windhorst, W. Beaino
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引用次数: 0

摘要

以免疫检查点抑制剂(如程序性细胞死亡受体(PD-1)及其配体(PD-L1))为靶点的免疫疗法为癌症治疗带来了革命性的变化。然而,众所周知,不同患者对 PD-1/PD-L1 免疫疗法的反应并不一致。目前的挑战是为每位患者量身定制治疗方案,而如果了解了 PD-1/PD-L1 的表达和动态变化,就有可能做到这一点。利用正电子发射断层扫描(PET)成像技术,可以在治疗过程中对这些免疫靶点进行无创和全系统成像。成功的 PET 成像示踪剂应符合有关靶点亲和力、特异性、清除率和靶点特异性摄取等方面的特定标准。这种示踪剂的结构特征将确定其特性,并可用于优化开发中的示踪剂和设计新的示踪剂。目前,已有一系列不同分子类别的 PD-1/PD-L1 靶向 PET 示踪剂,这些示踪剂在临床前和临床研究中都取得了令人瞩目的成果,但各有优缺点。本综述将概述目前针对 PD-1/PD-L1 轴的 PET 示踪剂。将讨论抗体、肽和抗体片段示踪剂的分子特征和结合特性以及优化它们的方法。
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Navigating the landscape of PD-1/PD-L1 imaging tracers: from challenges to opportunities
Immunotherapy targeted to immune checkpoint inhibitors, such as the program cell death receptor (PD-1) and its ligand (PD-L1), has revolutionized cancer treatment. However, it is now well-known that PD-1/PD-L1 immunotherapy response is inconsistent among patients. The current challenge is to customize treatment regimens per patient, which could be possible if the PD-1/PD-L1 expression and dynamic landscape are known. With positron emission tomography (PET) imaging, it is possible to image these immune targets non-invasively and system-wide during therapy. A successful PET imaging tracer should meet specific criteria concerning target affinity, specificity, clearance rate and target-specific uptake, to name a few. The structural profile of such a tracer will define its properties and can be used to optimize tracers in development and design new ones. Currently, a range of PD-1/PD-L1-targeting PET tracers are available from different molecular categories that have shown impressive preclinical and clinical results, each with its own advantages and disadvantages. This review will provide an overview of current PET tracers targeting the PD-1/PD-L1 axis. Antibody, peptide, and antibody fragment tracers will be discussed with respect to their molecular characteristics and binding properties and ways to optimize them.
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