Helmholtz Zentrum München (GmbH), Neuherberg, Germany, Institute of Biological and Medical Imaging.
Technical University of Munich, Germany, School of Medicine, Center for Translational Cancer Research (TranslaTUM), Chair of Biological Imaging.
Theranostics. 2021 Jun 26;11(16):7813-7828. doi: 10.7150/thno.56173. eCollection 2021.
Non-invasive monitoring of hemodynamic tumor responses to chemotherapy could provide unique insights into the development of therapeutic resistance and inform therapeutic decision-making in the clinic. Here, we examined the longitudinal and dynamic effects of the common chemotherapeutic drug Taxotere on breast tumor (KPL-4) blood volume and oxygen saturation using eigenspectra multispectral optoacoustic tomography (eMSOT) imaging over a period of 41 days. Tumor vascular function was assessed by dynamic oxygen-enhanced eMSOT (OE-eMSOT). The obtained optoacoustic data were thoroughly validated by cryoimaging and immunohistochemical staining against markers of vascularity and hypoxia. We provide the first preclinical evidence that prolonged treatment with Taxotere causes a significant drop in mean whole tumor oxygenation. Furthermore, application of OE-eMSOT showed a diminished vascular response in Taxotere-treated tumors and revealed the presence of static blood pools, indicating increased vascular permeability. Our work has important translational implications and supports the feasibility of eMSOT imaging for non-invasive assessment of tumor microenvironmental responses to chemotherapy.
非侵入性监测化疗引起的血流动力学肿瘤反应,可以为治疗耐药性的发展提供独特的见解,并为临床治疗决策提供信息。在这里,我们使用特征光谱多光谱光声断层扫描(eMSOT)成像,在 41 天的时间内,纵向和动态地研究了常见化疗药物多烯紫杉醇对乳腺肿瘤(KPL-4)血容量和氧饱和度的影响。通过动态氧增强 eMSOT(OE-eMSOT)评估肿瘤血管功能。通过对血管生成和缺氧标志物的冷冻成像和免疫组织化学染色,对获得的光声数据进行了彻底验证。我们提供了第一个临床前证据,表明 Taxotere 的长期治疗会导致整个肿瘤平均氧合作用显著下降。此外,OE-eMSOT 的应用显示 Taxotere 治疗的肿瘤中血管反应减弱,并显示存在静态血液池,表明血管通透性增加。我们的工作具有重要的转化意义,并支持 eMSOT 成像用于非侵入性评估化疗引起的肿瘤微环境反应的可行性。