IDH1 Mutations in Glioma: Considerations for Radiotracer Development.

Isocitrate dehydrogenases IDH1 and IDH2 are closely-related metabolic enzymes which catalyze the conversion of isocitrate to α-ketoglutarate (α-KG) by oxidative decarboxylation and simultaneously generate NADPH in cells. IDH1 and IDH2 are frequently mutated in WHO grade II and grade III gliomas and in secondary glioblastoma. In gliomas, IDH mutations are highly specific for the amino acid arginine in IDH1 enzyme’s substrate binding site, resulting in substitution of the arginine at 132 with histidine (R132H) in >80% of all IDH mutations [1]. IDH mutations result in production and accumulation of the metabolite D-2-hydroxyglutarate (D-2-HG) in IDH1 mutated cells, which greatly impacts the cellular metabolism and also contributes to tumor pathogenesis [2,3].