Evaluations of oxidative phosphorylation and glycolysis metabolism in tumors using PET/MRI

Tumor cells often show high uptake of glucose, which is used to feed the metabolic pathways of oxidative phosphorylation and glycolysis. Although glycolysis is often upregulated in tumor cells relative to normal tissues (known as the Warburg effect), oxidative phosphorylation may be upregulated or downregulated in tumors relative to normal tissues. Furthermore, the relative rates of oxidative phosphorylation vs. glycolysis within a tumor is often unknown. Importantly, different anti-cancer treatments that directly target or indirectly affect tumor metabolism change the rates of oxidative phosphorylation and glycolysis to different extents. Therefore, a method is needed to simultaneously interrogate oxidative phosphorylation and glycolysis in a tumor, to provide a more comprehensive assessment of tumor metabolism, and changes in metabolism caused by treatments.

We propose to use simultaneous PET/MRI to address this need. Translocator Protein (TSPO) is expressed on membranes of active mitochondria, and therefore TSPO expression is an excellent biomarker of upregulated oxidative phosphorylation in tumor cells. [F18]GE-180 is a new PET tracer that binds TSPO and has shown promise in differentiating tumors with high vs. low metabolic activities, presumably due to high vs. low levels of oxidative phosphorylation. Also, lactic acid is produced and secreted into the extracellular tumor microenvironment at the endpoint of glycolysis, and therefore extracellular acidosis is an excellent biomarker of glycolytic rate. AcidoCEST MRI is can measure tumor acidosis, which can be used to assess the level of tumor glycolysis. We are developing simultaneous PET/MRI to perform [F18]GE-180 PET in an attempt