Abstract #0780

Hyperpolarized 13C β-hydroxybutyrate/acetoacetate as a biomarker for non-invasive monitoring of NAD+/NADH status in glioblastoma

Chloe Najac¹, Marina Radoul¹, Lydia M Le Page^1,2, Georgios Batsios¹, Pavithra Viswanath¹, Anne Marie Gillespie¹, and Sabrina M Ronen¹

¹Department of Radiology and Biomedical Imaging, University of California San Francisco, San Francisco, CA, United States, ²Department of Physical Therapy and Rehabilitation Science, University of California San Francisco, San Francisco, CA, United States

Conversion of acetoacetate (AcAc) to β-hydroxybutyrate (β-HB) by the mitochondrial enzyme β-hydroxybutyrate dehydrogenase depends upon NADH availability. Previous studies have shown the potential of β-HB-to-AcAc ratio to reflect the redox state in rat hearts and lymphoma cells. Here, we assessed the value of HP [1,3-¹³C]-AcAc in brain. We demonstrated the potential to probe AcAc to β-HB conversion in normal mice and mice with glioblastoma. Significantly higher levels of [1-¹³C]-β-AcAc and [1-¹³C]-β-HB were observed in tumor-bearing mice compared to control mice. Consistent with lower levels of NADH measured in tumors, the [1-¹³C]-β-HB-to-[1-¹³C]-β-AcAc ratio trended towards a decrease compared to normal brain.

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