Department of Diagnostic and Interventional Radiology, School of Medicine & Klinikum rechts der Isar, Technical University of Munich, Munich, Germany.
Chair for Biological Imaging, School of Medicine & Klinikum rechts der Isar, Technical University of Munich, Munich, Germany.
Sci Rep. 2020 Mar 17;10(1):4903. doi: 10.1038/s41598-020-61191-z.
Most imaging studies of immunotherapy have focused on tracking labeled T cell biodistribution in vivo for understanding trafficking and homing parameters and predicting therapeutic efficacy by the presence of transferred T cells at or in the tumour mass. Conversely, we investigate here a novel concept for longitudinally elucidating anatomical and pathophysiological changes of solid tumours after adoptive T cell transfer in a preclinical set up, using previously unexplored in-tandem macroscopic and mesoscopic optoacoustic (photoacoustic) imaging. We show non-invasive in vivo observations of vessel collapse during tumour rejection across entire tumours and observe for the first time longitudinal tumour rejection in a label-free manner based on optical absorption changes in the tumour mass due to cellular decline. We complement these observations with high resolution episcopic fluorescence imaging of T cell biodistribution using optimized T cell labeling based on two near-infrared dyes targeting the cell membrane and the cytoplasm. We discuss how optoacoustic macroscopy and mesoscopy offer unique contrast and immunotherapy insights, allowing label-free and longitudinal observations of tumour therapy. The results demonstrate optoacoustic imaging as an invaluable tool in understanding and optimizing T cell therapy.
大多数免疫疗法的影像学研究都集中在追踪标记的 T 细胞在体内的生物分布，以了解迁移和归巢参数，并通过转移的 T 细胞在肿瘤部位或肿瘤内的存在来预测治疗效果。相反，我们在这里研究了一种新的概念，即在临床前环境中，通过以前未探索过的串联宏观和介观光声（超声）成像，对过继性 T 细胞转移后实体瘤的解剖和病理生理变化进行纵向阐明。我们显示了在整个肿瘤中观察到肿瘤排斥过程中血管塌陷的非侵入性体内观察，并首次观察到基于肿瘤内细胞减少导致的光吸收变化的无标记纵向肿瘤排斥。我们通过使用针对细胞膜和细胞质的两种近红外染料进行优化的 T 细胞标记，补充了 T 细胞生物分布的高分辨率荧光外显荧光成像。我们讨论了光声宏观和介观如何提供独特的对比和免疫治疗见解，允许对肿瘤治疗进行无标记和纵向观察。结果表明，光声成像是理解和优化 T 细胞治疗的宝贵工具。
