嵌合抗原受体 T 细胞 (CAR-T) 疗法已成为血液恶性肿瘤的变革性治疗策略。然而，其治疗实体瘤的功效仍然有限。深入全面地了解 CAR-T 细胞信号通路以及在肿瘤微环境中实时跟踪 CAR-T 细胞生物分布和激活的能力，将有助于设计下一代用于实体瘤的 CAR-T 细胞治疗。本综述总结了基于 CAR-T 细胞的免疫疗法中使用的信号网络以及细胞和分子成像工具和平台，涵盖体外和体内研究。首先，我们概述了对 CAR-T 细胞的激活和细胞毒性机制的现有理解，并与 T 细胞受体 (TCR) 信号通路的机制进行比较。我们进一步描述了活细胞成像常用的工具，以及最近的研究进展，重点是基因编码荧光蛋白（FP）和生物传感器。然后，我们讨论了多种体内成像方式的实用性，包括荧光和生物发光成像、磁共振成像 (MRI)、正电子发射断层扫描 (PET) 和光声 (PA) 成像，用于无创监测肿瘤内的 CAR-T 细胞动态组织，从而提供对治疗的优点和缺点的重要见解。最后，我们从影像学角度讨论了CAR-T细胞治疗当前的挑战和未来的方向。我们预计，全面、综合的 CAR-T 细胞成像方法将有助于在未来开发出更有效的实体瘤治疗方法。版权所有 © 2023。由 Elsevier B.V. 出版。

Chimeric Antigen Receptor T cell (CAR-T) therapy has emerged as a transformative therapeutic strategy for hematological malignancies. However, its efficacy in treating solid tumors remains limited. An in-depth and comprehensive understanding of CAR-T cell signaling pathways and the ability to track CAR-T cell biodistribution and activation in real-time within the tumor microenvironment will be instrumental in designing the next generation of CAR-T cells for solid tumor therapy. This review summarizes the signaling network and the cellular and molecular imaging tools and platforms that are utilized in CAR-T cell-based immune therapies, covering both in vitro and in vivo studies. Firstly, we provide an overview of the existing understanding of the activation and cytotoxic mechanisms of CAR-T cells, compared to the mechanism of T cell receptor (TCR) signaling pathways. We further describe the commonly employed tools for live cell imaging, coupled with recent research progress, with a focus on genetically encoded fluorescent proteins (FPs) and biosensors. We then discuss the utility of diverse in vivo imaging modalities, including fluorescence and bioluminescence imaging, Magnetic Resonance Imaging (MRI), Positron Emission Tomography (PET), and photoacoustic (PA) imaging, for noninvasive monitoring of CAR-T cell dynamics within tumor tissues, thereby providing critical insights into therapy's strengths and weaknesses. Lastly, we discuss the current challenges and future directions of CAR-T cell therapy from the imaging perspective. We foresee that a comprehensive and integrative approach to CAR-T cell imaging will enable the development of more effective treatments for solid tumors in the future.Copyright © 2023. Published by Elsevier B.V.