BIMG-09. GLUTAMINE AND GLYCINE BY MR SPECTROSCOPY IDENTIFY AGGRESSIVE GLIOMAS

Cancers reprogram their metabolism and the resulting alterations in metabolite abundance can be monitored in patients noninvasively using proton magnetic resonance spectroscopy (MRS). We evaluated glutamine, glycine and 2-hydroxyglutarate (2HG) in 27 adult subjects with gliomas (17 male and 10 female; age 22 - 69, median 39 years) using optimized MRS at 3T (PRESS TE 97ms) and examined their association with post-gadolinium enhancement, cell proliferation rate (MIB-1 labeling index), and overall survival of patients. The tumors included 9 glioblastomas (3 IDH mutated and 6 IDH wildtype), 10 astrocytomas (7 IDH mutated and 3 IDH wildtype), and 8 oligodendrogliomas (IDH mutated). The concentrations of glutamine and glycine were both significantly higher in enhancing tumors than in non-enhancing tumors (p=0.001 and 0.0001, respectively). The concentrations of glutamine and glycine were both positively correlated with MIB-1 (p=4E-5 and 1E-7, respectively). The sum of glutamine and glycine levels showed stronger association with MIB-1 (p=5E-10, r=0.89). In the Kaplan-Meier overall survival analysis, the survival was significantly shorter in patients with glutamine levels higher than 4.1 mM than those with concentrations less than 4.1 mM (p=0.02). For glycine, the patients with higher than 2.4 mM showed association with poor survival (p=0.03). The sum of glutamine and glycine levels showed stronger association with overall survival (p=0.008, cutoff 8.5mM). 2HG level greater than 0.5 mM was associated with long survival (p=0.01). We tested metabolic ratios to 2HG, in which 2HG estimates less than 1 mM were put as 1 mM (avoiding infinite ratios arising from null 2HG cases). The glutamine/2HG, glycine/2HG, and (glutamine+glycine)/2HG showed strong association with overall survival (p=2E-4, 2E-5 and 4.5E-7, respectively). Our data suggest that increased metabolism of glutamine and glycine is closely associated with rapid cell proliferation and poor survival, suggesting the metabolites are imaging biomarkers of glioma aggressiveness.