First in-human MR Metabolic Imaging of the Brain Using Hyperpolarized [1-13C]alpha-ketoglutarate

Motivation: Isocitrate dehydrogenase (IDH) mutational status is crucial for accurate diagnosis and prognosis of malignant gliomas. However, the current clinical assessment of IDH mutation requires an invasive brain biopsy for pathological testing. Goal(s): We aimed to perform first in-human MR studies using hyperpolarized [1-13C]alpha-ketoglutarate as a new probe of IDH mutational status via cancer metabolic reprogramming, along with cerebral bioenergetics. Approach: We acquired 13C MRS data from healthy brain volunteers (N=6) and glioma patients (N=6) who received hyperpolarized aKG. Results: Feasibility and safety were demonstrated in these 12 studies, with signals observed from [1-13C]alpha-ketoglutarate and its metabolite glutamate in the obtained 13C MRS data. Impact: MR molecular imaging with the new probe hyperpolarized [1-13C]alpha-ketoglutarate provided novel measurements of aKG metabolism and can investigate glioma IDH mutational status by detecting glutamate or the oncometabolite, 2-hydroxyglutarate.