Abstract #0891

Study of the Mutated Isocitrate Dehydrogenase 1 in Acute Myeloid Leukemia Using Hyperpolarized [1-13C]α-ketoglutaric Acid

Eugen Kubala^1,2,3, Kim A. Muñoz Álvarez¹, Oliver Dovey⁴, Steffen J. Glaser², Markus Schwaiger¹, George S. Vassiliou⁴, Roland Rad^5,6, Rolf F. Schulte³, and Marion I. Menzel³

¹Department of Nuclear Medicine, Klinikum Rechts der Isar, Technische Universität München, Munich, Germany, ²Department of Chemistry, Technische Universität München, Munich, Germany, ³General Electric Global Research, Munich, Germany, ⁴The Welcome Trust Sanger Institute, Hinxton/Cambridge, United Kingdom, ⁵Department of Medicine II, Klinikum Rechts der Isar, Technische Universität München, Munich, Germany, ⁶Cancer Consortium (DKTK), German Cancer Research Center (DKFZ), Munich, Germany

Previous studies suggest that isocitrate dehydrogenase 1 (IDH1) mutation plays a significant role in the cancerous metabolome. Among other alternations, expression of branched chain amino-acid transaminase 1 (BCAT1) is reduced, causing a decrease of α-ketoglutaric acid (αKG) to glutamic acid metabolic pathway. More importantly, the mutated IDH1 catalyzes a reaction of αKG to the oncometabolite 2-hydroxyglutarate. In this study we proved that these metabolic changes can be measured using hyperpolarized [1-¹³C]α-KG and ¹³Cmetabolic magnetic resonance spectroscopy (¹³CMMRS) in acute myeloid leukemia cell line in vitro.

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