11. Assessment of physico-chemical parameters of PDAC by non-invasive imaging during tumour progression and in response to therapeutically targeting pH-dependent processes
Modulation of the extracellular O2 and pH within the tumor microenvironment, but also of the intracellular pH within both, tumor- and stroma cells are believed to have a great impact on the course and outcome of the disease.
Within the project, we aim at:
- the validation of various optical pH and pO2 sensor probes, for their efficacy to monitor real time pH dynamics in vitro; probes, both with and without modification/functionalization with ligands will be developed together with the project partners and their sensitivity will be assessed in cell based assays and 3D cultures with adequate spatio-temporal resolution
- the validation of the probes to assess physico-chemical parameters by in vivo optical imaging in syngenic, transgenic or xenogenic murine and human PDAC models (including the pancreas-specific "pH-indicator” mouse) in different phases of PDAC progression
- analyzing how the measured chemical gradients (e.g. pH, pO2) within the PDAC and at the healthy pancreas-PDAC interface affect the tumor progression; the assessed physico-chemical parameters will be correlated e.g. to biomarker expression and hallmarks of PDAC progression analyzed by non-invasive imaging techniques (MRI, optical imaging, CT) and microscopy
- implementation of the developed sensor-probes to develop and optimize pH-modulating treatment strategies and transportome-based (nano-)therapeutic concepts
- monitoring changes in PDAC progression in response to the selected therapies developed together with different project partners
- transferring the developed concepts into pre-/clinical application.