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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