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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