Abstract #3717

Developing a therapeutic strategy for a glycolytic cancer model by monitoring on-target in vivo efficacy of a newly developed LDH inhibitor using hyperpolarized 13C Magnetic Resonance Imaging

Nobu Oshima¹, Shun Kishimoto¹, Krisitin Beebe¹, Dan Crooks¹, Kazutoshi Yamamoto¹, Jeffery R. Brender¹, Ganesha Rai², Daniel Urban², Goria Benavides³, Giuseppe Squadrito³, Victor Darley-Usmar³, Matt Hall², James B. Mitchell¹, Murali C. Krishna¹, and Leonard M. Neckers¹

¹NCI/NIH, Bethesda, MD, United States, ²National Center for Advancing Translational Sciences (NCATS), NIH, Rockville, MD, United States, ³University of Alabama School of Medicine, Birmingham, AL, United States

This study aimed to develop a new therapeutic strategy with a novel Lactate Dehydrogenase A inhibitor (LDHi) for cancers bearing the Warburg phenotype by monitoring the impact on in vivo metabolic flux of the LDHi using hyperpolarized ¹³C-MRI. ¹³C-MRI with hyperpolarized [1-¹³C]pyruvate revealed in vivo pharmacodynamics and an effective dose of the LDHi without the need for tissuse sampling. In addition, based on these results, we developed a therapeutic strategy with the LDHi for mice harboring a MiaPaCa-2 (a glycolytic pancreatic cancer cell line) xenograft. This methodology can be a novel approach to treat glycolytic cancers.

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