Institute of Molecular Enzyme Technology (IMET), Heinrich Heine University Düsseldorf, Forschungszentrum Jülich GmbH, Jülich, 52425, Germany.
Institute of Biological and Medical Imaging (IBMI), Helmholtz Zentrum München, Neuherberg, 85764, Germany.
Nat Commun. 2019 Mar 13;10(1):1191. doi: 10.1038/s41467-019-09081-5.
Τhe morphology, physiology and immunology, of solid tumors exhibit spatial heterogeneity which complicates our understanding of cancer progression and therapy response. Understanding spatial heterogeneity necessitates high resolution in vivo imaging of anatomical and pathophysiological tumor information. We introduce Rhodobacter as bacterial reporter for multispectral optoacoustic (photoacoustic) tomography (MSOT). We show that endogenous bacteriochlorophyll a in Rhodobacter gives rise to strong optoacoustic signals >800 nm away from interfering endogenous absorbers. Importantly, our results suggest that changes in the spectral signature of Rhodobacter which depend on macrophage activity inside the tumor can be used to reveal heterogeneity of the tumor microenvironment. Employing non-invasive high resolution MSOT in longitudinal studies we show spatiotemporal changes of Rhodobacter spectral profiles in mice bearing 4T1 and CT26.WT tumor models. Accessibility of Rhodobacter to genetic modification and thus to sensory and therapeutic functions suggests potential for a theranostic platform organism.
实体瘤的形态、生理学和免疫学表现出空间异质性，这使得我们对癌症进展和治疗反应的理解变得复杂。要理解这种空间异质性，就需要对解剖学和病理生理学肿瘤信息进行高分辨率的体内成像。我们引入了红色硫细菌作为多谱段光声（超声）断层扫描（MSOT）的细菌报告基因。我们发现，红色硫细菌内源性细菌叶绿素 a 会在远离干扰性内源性吸收体的 800nm 处产生强烈的光声信号。重要的是，我们的结果表明，红色硫细菌的光谱特征会发生变化，而这种变化取决于肿瘤内的巨噬细胞活性，可用于揭示肿瘤微环境的异质性。在纵向研究中采用非侵入性高分辨率 MSOT，我们在携带 4T1 和 CT26.WT 肿瘤模型的小鼠中观察到了红色硫细菌光谱特征的时空变化。红色硫细菌易于进行基因修饰，因此具有感知和治疗功能，这表明它有可能成为一种治疗诊断两用的平台生物。
