Combined biochemical and biophysical imaging biomarkers for characterization of tumor metabolism and response to therapy

结合生化和生物物理成像生物标志物，用于表征肿瘤代谢和治疗反应

• 批准号: 391523415
• 负责人: Professor Dr. Franz Schilling
• 金额: --
• 依托单位: Klinik und Poliklinik für Nuklearmedizin
• 依托单位国家: 德国
• 项目类别: Independent Junior Research Groups
• 财政年份: 2017
• 资助国家: 德国
• 起止时间: 2016-12-31 至 2022-12-31
• 项目状态: 已结题
• 来源: https://gepris.dfg.de/gepris/projekt/391523415?language=en
• 关键词: Combined; biochemical; biophysical; imaging; biomarkers

Imaging biomarkers enable a comprehensive characterization of tissue providing functional, physiological, metabolic, cellular and molecular information beyond anatomical structures. For cancer patients, specific non-invasive imaging strategies for early-stage detection, tumor phenotyping and evaluation of response to therapy are not available at a satisfactory level, creating a pressing need for advanced technologies. In this project, I aim to develop two novel non-invasive imaging techniques to measure extracellular pH and transmembrane water permeability in tumors. First, by using pH imaging, we want to characterize the acidic tumor microenvironment caused by aberrant metabolism and study the link to tumor aggressiveness and tumor response to treatment. Second, we will test whether imaging of transmembrane water permeability reports on early stages of cell death, thereby providing an early evaluation technology to detect whether a drug has hit its target before an anatomical reduction in tumor size is recognizable. Specifically, we will advance current methods for non-invasive MRI pH imaging using novel hyperpolarized 13C-labelled biosensors and new MRI acquisition schemes for 3D pH imaging. Faster and more sensitive protocols for transmembrane water exchange MRI measurements in vitro and in vivo will be developed allowing 3D mapping of the apparent exchange rate (AXR). Both pH imaging and AXR mapping can help to elucidate tumor biology, allowing to characterize tumor metabolic phenotype and to detect early treatment response non-invasively.

成像生物标志物能够对组织进行全面的表征，提供解剖结构之外的功能、生理、代谢、细胞和分子信息。对于癌症患者来说，用于早期检测、肿瘤表型分析和治疗反应评估的特定非侵入性成像策略尚未达到令人满意的水平，因此迫切需要先进技术。在这个项目中，我的目标是开发两种新颖的非侵入性成像技术来测量肿瘤的细胞外 pH 值和跨膜水渗透性。首先，通过使用 pH 成像，我们想要表征异常代谢引起的酸性肿瘤微环境，并研究与肿瘤侵袭性和肿瘤对治疗反应的联系。其次，我们将测试跨膜水渗透性成像是否报告细胞死亡的早期阶段，从而提供一种早期评估技术，以在可识别肿瘤尺寸的解剖学缩小之前检测药物是否已达到其目标。具体来说，我们将使用新型超极化 13C 标记生物传感器和用于 3D pH 成像的新 MRI 采集方案来推进当前的非侵入性 MRI pH 成像方法。将开发更快、更灵敏的体外和体内跨膜水交换 MRI 测量方案，以实现表观交换率 (AXR) 的 3D 绘图。 pH 成像和 AXR 图谱都有助于阐明肿瘤生物学，从而能够表征肿瘤代谢表型并以非侵入方式检测早期治疗反应。