Non-invasive in vivo assessment of IDH1 mutational status in glioma

Myriam M. Chaumeil, Peder E. Z. Larson, Hikari A. I. Yoshihara, Olivia M. Danforth, Daniel B. Vigneron, Sarah J. Nelson, Russell O. Pieper, Joanna J. Phillips and Sabrina M. Ronen ()
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Myriam M. Chaumeil: University of California San Francisco
Peder E. Z. Larson: University of California San Francisco
Hikari A. I. Yoshihara: University of California San Francisco
Olivia M. Danforth: University of California San Francisco
Daniel B. Vigneron: University of California San Francisco
Sarah J. Nelson: University of California San Francisco
Russell O. Pieper: Brain Tumor Research Center, University of California San Francisco
Joanna J. Phillips: Brain Tumor Research Center, University of California San Francisco
Sabrina M. Ronen: University of California San Francisco

Nature Communications, 2013, vol. 4, issue 1, 1-12

Abstract: Abstract Gain-of-function mutations of the isocitrate dehydrogenase 1 (IDH1) gene are among the most prevalent in low-grade gliomas and secondary glioblastoma. They lead to intracellular accumulation of the oncometabolite 2-hydroxyglutarate, represent an early pathogenic event and are considered a therapeutic target. Here we show, in this proof-of-concept study, that [1-13C] α-ketoglutarate can serve as a metabolic imaging agent for non-invasive, real-time, in vivo monitoring of mutant IDH1 activity, and can inform on IDH1 status. Using 13C magnetic resonance spectroscopy in combination with dissolution dynamic nuclear polarization, the metabolic fate of hyperpolarized [1-13C] α-ketoglutarate is studied in isogenic glioblastoma cells that differ only in their IDH1 status. In lysates and tumours that express wild-type IDH1, only hyperpolarized [1-13C] α-ketoglutarate can be detected. In contrast, in cells that express mutant IDH1, hyperpolarized [1-13C] 2-hydroxyglutarate is also observed, both in cell lysates and in vivo in orthotopic tumours.

Date: 2013
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DOI: 10.1038/ncomms3429

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