Krutzek Fabian, Kopka Klaus, Stadlbauer Sven
Department of Translational TME Ligands, Institute of Radiopharmaceutical Cancer Research, Helmholtz Center Dresden-Rossendorf, 01328 Dresden, Germany.
School of Science, Faculty of Chemistry and Food Chemistry, Technical University Dresden, 01069 Dresden, Germany.
Pharmaceuticals (Basel). 2022 Jun 14;15(6):747. doi: 10.3390/ph15060747.
Immune checkpoint inhibitor (ICI) therapy has emerged as a major treatment option for a variety of cancers. Among the immune checkpoints addressed, the programmed death receptor 1 (PD-1) and its ligand PD-L1 are the key targets for an ICI. PD-L1 has especially been proven to be a reproducible biomarker allowing for therapy decisions and monitoring therapy success. However, the expression of PD-L1 is not only heterogeneous among and within tumor lesions, but the expression is very dynamic and changes over time. Immunohistochemistry, which is the standard diagnostic tool, can only inadequately address these challenges. On the other hand, molecular imaging techniques such as positron emission tomography (PET) and single-photon emission computed tomography (SPECT) provide the advantage of a whole-body scan and therefore fully address the issue of the heterogeneous expression of checkpoints over time. Here, we provide an overview of existing PET, SPECT, and optical imaging (OI) (radio)tracers for the imaging of the upregulation levels of PD-1 and PD-L1. We summarize the preclinical and clinical data of the different molecule classes of radiotracers and discuss their respective advantages and disadvantages. At the end, we show possible future directions for developing new radiotracers for the imaging of PD-1/PD-L1 status in cancer patients.
免疫检查点抑制剂（ICI）疗法已成为多种癌症的主要治疗选择。在已涉及的免疫检查点中，程序性死亡受体1（PD-1）及其配体PD-L1是ICI的关键靶点。PD-L1尤其被证明是一种可重复的生物标志物，可用于指导治疗决策和监测治疗效果。然而，PD-L1的表达不仅在肿瘤病灶之间和内部存在异质性，而且这种表达非常动态，会随时间变化。免疫组织化学作为标准的诊断工具，只能不完全应对这些挑战。另一方面，正电子发射断层扫描（PET）和单光子发射计算机断层扫描（SPECT）等分子成像技术具有全身扫描的优势，因此能充分解决检查点随时间变化的异质性表达问题。在此，我们概述了现有的用于成像PD-1和PD-L1上调水平的PET、SPECT和光学成像（OI）（放射性）示踪剂。我们总结了不同分子类别的放射性示踪剂的临床前和临床数据，并讨论了它们各自的优缺点。最后，我们展示了开发用于癌症患者PD-1/PD-L1状态成像的新型放射性示踪剂的可能未来方向。
