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Abstract #4474

Metabolic reprogramming in a relevant IDH1-mutated human glioma xenograft model

Tom Peeters1, Krissie Lenting2, Jack van Asten1, William Leenders2, and Arend Heerschap1

1Radiology and Nuclear Medicine, Radboud university medical center, Nijmegen, Netherlands, 2Pathology, Radboud university medical center, Nijmegen, Netherlands

Understanding metabolic aberrations in IDH-mutated gliomas requires xenograft models growing in a relevant tissue microenvironment and resembling its human genetic counterparts. We performed in vivo 1H MRSI of human-derived oligodendroglioma xenograft models to map lactate and total choline concentrations. Lactate levels were significantly lower and total choline higher in mutated tumor tissue compared to non-tumor brain in the same animal, or to its wild-type counterpart model. This outcome was correlated with expression levels of enzymes and transporters in both lactate- and phospholipid-related metabolic pathways. The findings point to a metabolic reprogramming of aerobic glycolysis and lipid synthesis by the IDH1 mutation.

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