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

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变化与凋亡诱导之间的联系。因此，肿瘤细胞在体外用基于生物发光的凋亡报告基因构建体稳定转染，并用全氟化碳（PFC）标记。PFC容易溶解氧，这会以与绝对氧分压（pO 2）成正比的方式改变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，在抗癌治疗过程中，可以通过生物发光成像监测caspase-3/7活化，并且可以通过19-Fluoro-MRI定量氧合水平的变化。通过同时监测这两个生理肿瘤参数，可以阐明新兴的抗癌疗法如用工程化T细胞的免疫疗法的作用模式，以直接显示对治疗的应答。因此，这些非侵入性测量是治疗功效的潜在有价值的生物标志物。

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.