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Abstract #3604

Imaging branched-chain amino acid metabolism in glioma using hyperpolarized [1-13C] alpha-ketoisocaproate

Eul Hyun Suh1, Weijun Ou1,2, Ian Corbin1, Dean Sherry1,3, and Jae Mo Park1

1Advanced Imaging Research Center, University of Texas Southwestern Medical Center, Dallas, TX, United States, 2Organ Transplantation Center, Sun Yat-sen University, Guangzhou, People's Republic of China, 3Chemistry, University of Texas Dallas, Richardson, TX, United States

Upregulated branched-chain amino transaminase 1 (BCAT1) expression is a common metabolic feature of most primary cancers with wild-type isocitrate dehydrogenase (IDH), including glioblastoma. In this study, 13C-labeled a-ketoisocaproate (KIC) metabolism was investigated in a brain tumor-bearing rat to assess BCAT1 and branched-chain α-ketoacid dehydrogenase (BCKDH) activities in the tumor. Following an intravenous bolus injection of hyperpolarized [1-13C]KIC, both [1-13C]leucine and 13C-bicarbonate were observed in the brain. We observed less [1-13C]leucine but greater bicarbonate production in the tumor compared to normal, healthy brain tissue, suggesting downregulated chemical exchange of [1-13C]KIC with leucine catalyzed by BCAT1 and upregulated BCKDH activity, respectively.

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