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

• Applicant: Thomas Weber
• Subject Area: Nuclear Medicine, Radiotherapy, Radiobiology ; Pharmacology ; Cell Biology
• Term: from 2014 to 2015
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 268851506

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.

• DFG Programme: Research Fellowships
• International Connection: USA
• Host: Professor Eric T. Ahrens, Ph.D.