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

该博士后项目的目的是阐明抗癌治疗(化疗、基因治疗或免疫治疗)后小鼠肿瘤细胞内氧合水平的变化与诱导细胞凋亡之间的联系。因此，基于生物发光的凋亡报告构建和全氟化碳(PFC)体外标记可稳定地转染肿瘤细胞。PFC很容易溶解氧气，这会改变19-氟信号的磁共振成像(MRI)特性，与绝对氧分压(PO2)成正比。将这些肿瘤细胞接种到受试者体内后，通过生物发光成像可以监测到细胞凋亡诱导(caspase-3/7激活)，通过19-氟-磁共振成像可以量化抗癌治疗过程中氧合水平的变化。通过同时监测这两个生理肿瘤参数，可以阐明新兴抗癌治疗的作用模式，如工程T细胞免疫治疗，以直接显示治疗反应。因此，这些非侵入性测量是潜在的有价值的治疗效果的生物标志物。

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.