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

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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.