HP DHA was demonstrated as an imaging agent for probing the biochemical response to ascorbate therapy in patient derived xenograft (PDX) models of cancer. Changes in DHA/ascorbate metabolism were observed in PDX tumors after prolonged treatment, mirroring the observed treatment response to high dose ascorbate. Metabolomic studies showed that high dose ascorbate therapy induced oxidative stress, leading to increased flux through the pentose phosphate pathway (PPP). DNA damage repair mutants exhibit lower baseline flux through the PPP and are more sensitized to ascorbate induced ROS. These results demonstrate a new method for assessing oxidative stress in vivo using HP DHA.
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