hyperpolarized carbon 13 alpha-ketoglutarate

A radioconjugate and dynamic nuclear polarization (DNP) metabolic imaging probe composed of hyperpolarized alpha-ketoglutarate (aKG) labeled with carbon C 13, with potential usage in the diagnostic imaging of isocitrate dehydrogenase 1 (IDH1) mutant-expressing cancer cells upon magnetic resonance imaging (MRI). Upon administration, hyperpolarized carbon C 13 aKG (HP 13C-aKG) is taken up by IDH1-expressing cancer cells. In tumors that express wild-type IDH1, only HP 13C-aKG can be detected. In cells that express mutant IDH1, HP 13C-aKG is further metabolized to HP 13C-2-hydroxyglutarate (HP 13C-2-HG) while not in tumor cells expressing wild-type IDH1 or in normal, healthy brain tissue. Upon nuclear magnetic resonance (NMR)-based imaging, HP 13C-aKG is detected in wild-type IDH1-expressing cancer cells, and both HP 13C-aKG and HP 13C-2-HG can be detected in IDH1 mutant-expressing cancer cells though HP 13C-aKG detection decreases in IDH1-mutant-expressing cancer cells over time due to conversion to HP 13C-2-HG. This may aid in the diagnosis of cancers expressing IDH1 and provides mutant IDH1 status of tumor cells.