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Abstract #0040

Deuterium-labeled α-ketoglutarate enables metabolic imaging of the isocitrate dehydrogenase mutation in brain tumors.

Celine Taglang1, Georgios Batsios1, Anne-Marie Gillespie1, and Pavithra Viswanath1
1Radiology, UCSF, San Francisco, CA, United States

Synopsis

Keywords: Deuterium, Deuterium, Contrast mechanisms, Preclinical.

Motivation: Mutations in isocitrate dehydrogenase (IDHm) define a distinct molecular class of gliomas. IDHm converts the normal metabolite α-ketoglutarate to the oncometabolite D-2-hydroxyglutarate (D-2HG), which drives tumorigenesis.

Goal(s): The IDHm inhibitor vorasidenib was recently approved for treatment of IDHm glioma patients. However, non-invasive methods of imaging IDHm activity in vivo are lacking.

Approach: Here, we show that deuterium metabolic imaging using diethyl-[3,3’-2H]-α-ketoglutarate allows quantification of D-2HG production and visualization of tumor burden specifically in mice bearing IDHm but not IDH wild-type gliomas.

Results: Importantly, diethyl-[3,3’-2H]-α-ketoglutarate provides an early response to vorasidenib that precedes MRI-detectable volumetric alterations in mice bearing intracranial IDHm gliomas in vivo

Impact: Our studies provide proof-of-concept evidence that diethyl-[3,3’-2H]-α-ketoglutarate informs on tumor burden and treatment response in IDHm gliomas. Clinical translation of diethyl-[3,3’-2H]-a-ketoglutarate will provide clinicians with a tool to monitor disease progression in IDHm glioma patients, which is currently challenging.

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