Abstract #3081

Evaluation of the in vivo on-target effect of a newly developed LDH inhibitor using hyperpolarized 13C Magnetic Resonance Spectroscopic Imaging

Nobu Oshima¹, Shun Kishimoto², Keita Saito², Dan Crooks³, Kristin Beebe³, Kazutoshi Yamamoto², Jeffery Brender², Ganesha Rai⁴, Bryan T Mott⁴, David J Maloney⁴, James B Mitchell², Murali K Cherukuri², and Leonard M Neckers³

¹RBB,UOB/NCI, NIH, Bethesda, MD, United States, ²RBB/NCI, NIH, Bethesda, MD, United States, ³UOB/NCI, NIH, Bethesda, MD, United States, ⁴National Center for Advancing Translational Sciences (NCATS), NIH, Rockville, MD, United States

This study aimed to monitor the impact on metabolic flux in vivo of a newly developed Lactate Dehydrogenase A Inhibitor (LDHI), using hyperpolarized 13C Magnetic Resonance (MR) technology. Using hyperpolarized 13C MR Spectroscopy and Chemical Shift imaging, we found that the LDHI significantly and rapidly suppressed the [1-13C]lactate to [1-13C]pyruvate ratio after single dose administration to mice harboring a MiaPaca (a glycolytic pancreatic cancer cell line) xenograft. These results indicate that the LDHI suppressed lactate production in the tumors. Thus, using Hyperpolarized 13C MRI provides a very useful technology to evaluate in vivo on-target efficacy of LDH inhibitors.

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