Simple Esterification of [1-<sup>13</sup>C]-Alpha-Ketoglutarate Enhances Membrane Permeability and Allows for Noninvasive Tracing of Glutamate and Glutamine Production
Jenna E. AbuSalim, Kazutoshi Yamamoto, Natsuko Miura, Burchelle Blackman, Jeffrey Brender, Chandrasekhar Mushti, Tomohiro Seki, Kevin Camphausen, Rolf E. Swenson, Murali C. Krishna, Aparna H. Kesarwala
Abstract
Alpha-ketoglutarate (α-KG) is a key metabolite and signaling molecule in cancer cells, but the low permeability of α-KG limits the study of α-KG mediated effects in vivo. Recently, cell-permeable monoester and diester α-KG derivatives have been synthesized for use in vivo, but many of these derivatives are not compatible for use in hyperpolarized carbon-13 nuclear magnetic resonance spectroscopy (HP-13C-MRS). HP-13C-MRS is a powerful technique that has been used to noninvasively trace labeled metabolites in real time. Here, we show that using diethyl-[1-13C]-α-KG as a probe in HP-13C-MRS allows for noninvasive tracing of α-KG metabolism in vivo.