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Abstract #3717

Developing a therapeutic strategy for a glycolytic cancer model by monitoring on-targetĀ 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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