In the last decade, monoclonal antibodies (mAbs) targeting CTLA-4, PD-1, or PD-L1 have been developed and immune checkpoint inhibitors (ICIs) have become the main approach in cancer immunotherapy. However, not all patients benefit from ICI therapy and some are at risk of developing treatment-induced side-effects. These aspects, in parallel with the imaging challenges related to response assessments during immunotherapy, have driven scientific research to the discovery of new predictive biomarkers to individualize patients who could benefit from ICIs. In this context, molecular imaging using PET (positron emission tomography), which allows for whole-body tumor visualization, may be a promising non-invasive method for the determination of patients’ sensitivity to antibody drugs. Several PET tracers, diverse from 2-[18F]FDG (or 2-Deoxy-2-[18F]fluoroglucose), have been developed to image immune checkpoints (ICs) or key elements of the immune system, although most of them are still in preclinical phases. Herein, we present the current state of the ImmunoPET-targeting of IC proteins with mAbs and antibody fragments, with a main focus on the latest developments in clinical molecular imaging studies of solid tumors. Moreover, given the relevance of the immune system and of tumor-infiltrating lymphocytes in particular in the prediction of the benefit of ICIs, we dedicate a portion of this review to ImmunoPET-targeting T cells.
过去十年间，针对CTLA-4、PD-1或PD-L1的单克隆抗体（mAbs）相继问世，免疫检查点抑制剂（ICIs）已成为癌症免疫治疗的主要手段。然而，并非所有患者都能从ICI治疗中获益，部分患者还存在发生治疗相关副作用的风险。这些现实问题，加之免疫治疗期间疗效评估相关的影像学挑战，共同推动了新型预测性生物标志物的科学研究，以期筛选出可能受益于ICIs的个体患者。在此背景下，能够实现全身肿瘤可视化的PET（正电子发射断层扫描）分子影像技术，可能成为评估患者对抗体药物敏感性的有前景的无创检测方法。目前已有多种不同于2-[18F]FDG（2-脱氧-2-[18F]氟代葡萄糖）的PET示踪剂被开发用于免疫检查点（ICs）或免疫系统关键元件的成像，尽管大多数仍处于临床前研究阶段。本文重点综述了以单克隆抗体及其片段为载体的免疫检查点蛋白靶向免疫PET显像的研究现状，主要聚焦实体瘤临床分子影像研究的最新进展。此外，鉴于免疫系统特别是肿瘤浸润淋巴细胞在预测ICIs疗效中的重要意义，本综述还专门探讨了T细胞靶向免疫PET显像的研究进展。
Clinical Application of ImmunoPET Targeting Checkpoint Inhibitors
肿瘤(癌症)患者之家