Abstract #0676

Hyperpolarized [1-13C]pyruvate detects brain glucose metabolism and sex-specific vulnerability in glucose transporter deficient mice

Caroline Guglielmetti^1,2, Huihui Li³, Lydia M. Le Page^1,2, Lauren Y. Shields³, Jeffrey C. Rathmell⁴, Ken Nakamura³, and Myriam M. Chaumeil^1,2

¹Department of Physical Therapy and Rehabilitation Science, University of California San Francisco, San Francisco, CA, United States, ²Department of Radiology and Biomedical Sciences, University of California San Francisco, San Francisco, CA, United States, ³Gladstone Institute of Neurological Disease, San Francisco, CA, United States, ⁴Vanderbilt Center for Immunobiology, Department of Pathology, Microbiology, and Immunology, Vanderbilt University Medical Center, Nashville, TN, United States

We used hyperpolarized ¹³C magnetic resonance spectroscopic imaging (HP ¹³C MRSI), fluorine-18 fluorodeoxyglucose (¹⁸F-FDG) positron emission tomography (PET) imaging and T₂-weighted MRI to detect brain glucose metabolism in mice harboring deletion of the glucose transporter 3 (GLUT3) in CA1 hippocampal neurons. GLUT3 deletion induced memory impairment in males and females, highlighting the importance of glucose uptake by neurons. HP [1-¹³C]lactate-to-pyruvate ratios and brain volumes were decreased in female GLUT3 deficient mice, but not in males, indicating sex-specific vulnerability. No changes were detected using ¹⁸F-FDG PET imaging, highlighting the potential of HP [1-¹³C]pyruvate to detect downstream alterations in brain glucose metabolism.

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