Image-Guide Tumor Therapy with Innovative Quantitative Deuterium Metabolic MR Imaging
DFG Project
Metabolism plays a crucial role in the origin and development of several relevant diseases, including neurodegeneration, cardiovascular, diabetes, and cancer. Cancer mutations that result in metabolic reprogramming of the tissue microenvironment have been associated to tumor therapy resistance, relapse, and metastasis. For instance, despite the considerable progress in innovative checkpoint immunotherapies (CPI), most solid cancers still fail to respond to most CPI trials. Recently, literature associates these observations to the immunosuppressive role of the local tumor microenvironment (TME) and tumor heterogeneity. Currently, in clinics, the only available techniques to routinely monitor glucose metabolism are 1) positron emission tomography (PET) with the application of the radioactive FDG) and, 2) hyperpolarized magnetic resonance spectroscopic imaging (HPMRSI) with the injection of pyruvate. Although these techniques are quite powerful and complementary, they do not show the metabolism downstream of glucose uptake (FDG-PET). They also do not provide quantitative information about metabolism (HPMRSI). Deuterium metabolic MR imaging (dMI) is a novel technology capable of providing quantitative measures of the local tissue metabolism. dMI uses safe 2H-labeled substrates (e.g. [6,6′-2H2]glucose and [2H3]acetate) to generate metabolic maps. This technique has enormous clinical potential, and its implementation in Tübingen will be a huge step forward to functionally image-guided tumor therapies in animals and humans.