Non-invasive monitoring of the interplay between intracellular oxygen levels and apoptosis induction in mouse tumors during immunotherapy and gene therapy by 19-fluorine-MRI and bioluminescence imaging

通过 19-氟 MRI 和生物发光成像无创监测免疫治疗和基因治疗期间小鼠肿瘤细胞内氧水平与细胞凋亡诱导之间的相互作用

• 批准号: 268851506
• 负责人: Thomas Weber
• 金额: --
• 依托单位: Department of Radiology
• 依托单位国家: 德国
• 项目类别: Research Fellowships
• 财政年份: 2014
• 资助国家: 德国
• 起止时间: 2013-12-31 至 2014-12-31
• 项目状态: 已结题
• 来源: https://gepris.dfg.de/gepris/projekt/268851506?language=en
• 关键词: Non; invasive; monitoring; interplay; between

The aim of the postdoctoral project is to elucidate the connection between changes in the intracellular oxygenation level and the apoptosis induction in mouse tumors after anti-cancer therapy (chemotherapy, gene therapy, or immunotherapy). Therefore, tumor cells are stably transfected with a bioluminescence-based apoptosis reporter construct and labeled with perfluorocarbons (PFC) ín vitro. PFC readily dissolve oxygen, which alters the magnetic resonance imaging (MRI) property of the 19-fluorine signal in a directly proportional manner to the absolute partial oxygen pressure (pO2). After inoculation of those tumor cells into the subject, apoptosis induction (caspase-3/7 activation) can be monitored by bioluminescence imaging and changes in oxygenation level can be quantified by 19-fluorine-MRI during anticancer treatment.By monitoring those two physiological tumor parameter simultaneously, the mode of action of emerging anticancer therapies such as immunotherapy with engineered T cells can be elucidated to directly show responses to treatment. Therefore, those non-invasive measurements are potentially valuable biomarkers for therapeutic efficacy.

本博士后项目的目的是阐明小鼠肿瘤在接受抗癌治疗（化疗、基因治疗或免疫治疗）后，细胞内氧合水平的变化与细胞凋亡诱导之间的关系。因此，用基于生物发光的凋亡报告基因构建物稳定转染肿瘤细胞，并用全氟化碳（PFC） ín体外标记。PFC容易溶解氧气，这与绝对分氧压（pO2）成正比地改变了19-氟信号的磁共振成像（MRI）特性。将这些肿瘤细胞接种到受试者体内后，通过生物发光成像监测细胞凋亡诱导（caspase-3/7激活），并通过19-氟磁共振成像定量测定抗肿瘤治疗过程中氧合水平的变化。通过同时监测这两种肿瘤生理参数，可以阐明新兴抗癌疗法的作用模式，如工程T细胞免疫疗法，从而直接显示对治疗的反应。因此，这些非侵入性测量是治疗效果的潜在有价值的生物标志物。