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Abstract #1151

Deuterium metabolic imaging of response to precision therapy in BRAF-V600E mutant gliomas

Georgios Batsios1, Suresh Udutha1, Anne Marie Gillespie1, Claudia Petritsch2, Sabine Mueller1, and Pavithra Viswanath1
1University of Caifornia, San Francisco, San Francisco, CA, United States, 2Stanford University, Stanford, CA, United States

Synopsis

Keywords: Biomarkers, Deuterium, preclinical, BRAF mutation, [6,6'-2H]glucose

Motivation: Oncogenic BRAF-V600E mutations are common in gliomas in adults and children. The combination of the BRAF-V600E inhibitor dabrafenib and the MEK1/2 inhibitor trametinib improves patient survival. However, there is considerable variation in the durability of response, underscoring the need for early biomarkers of treatment response.

Goal(s): To determine whether dabrafenib/trametinib induces alterations in glucose metabolism that can be leveraged for non-invasive imaging.

Approach: Usage of DMI in clinically relevant BRAF-V600E models

Results: We show that DMI-detectable lactate production from [6,6’-2H]-glucose provides an early readout of response to therapy that precedes volumetric alterations and predicts extended survival in vivo.

Impact: Our studies mechanistically link BRAF/MEK inhibition with downregulation of glycolysis and identify [6,6’-2H]-glucose as a novel contrast agent for imaging early response to therapy. Clinical translation of our studies will enable precision imaging of response to therapy for BRAF-mutant gliomas.

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Keywords