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Abstract #0923

Imaging ascorbate-mediated oxidative stress in PDX models of pancreatic cancer

Nathaniel Kim1, Arsen Mamakhantan1, Kristin Granlund1, Elisa de Stanchina2, Manish Shah3, Lewis Cantley4, and Kayvan R. Keshari1
1Department of Radiology, Memorial Sloan Kettering Cancer Center, New York, NY, United States, 2Antitumor Assessment Core Facility, Molecular Pharmacology Program, Memorial Sloan Kettering Cancer Center, New York, NY, United States, 3Weill Cornell Medicine, New York-Presbyterian Hospital, New York, NY, United States, 4Meyer Cancer Center, Department of Medicine, Well Cornell Medical College, New York, NY, United States

We investigated hyperpolarized [1-13C] dehydroascorbic acid (HP DHA) as an imaging agent for probing oxidative stress in patient derived xenograft models (PDXs) of pancreatic cancer. By increasing the T1 via D­2O solvation and increasing the dose administered via awake mouse injection, conversion of DHA to ascorbate was readily observed in KRAS and BRCA mutant cancers. HP DHA was then used to characterize oxidative stress in these PDX models and their biochemical mechanism of response to ascorbate therapy. Changes in DHA/ascorbate metabolism were measured in these tumor models, demonstrating a proof of concept method for assessing ascorbate therapy in pancreatic cancer.

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