A kinetic model to quantify 2-hydroxyglutarate when using hyperpolarized [1-13C]Α-ketoglutarate to detect mutant IDH1 in low grade gliomas

We introduce a kinetic modeling framework to detect glutamate and 2-hydroxyglutarate (2HG) production from hyperpolarized [1-¹³C]alpha-ketoglutarate (C1aKG). Detection of 2HG in vivo is often confounded with [5-¹³C]alpha-ketoglutarate (C5aKG), a natural abundance peak. We employ the model, based on the solution to differential equations of a three-site model, to separately detect 2HG from C5aKG. To test the model, we used cell lysate data where separate signal peaks of 2HG and C5aKG were experimentally measured. Cases with inputs of 2HG alone, 2HG+C5aKG, and C5aKG alone were evaluated to validate the model.