biostudies-literatureAbuSalim JENational Cancer InstituteNCI NIH HHSNational Institutes of Health Intramural Research ProgramJapan Society for the Promotion of Science2144-2150https://www.ebi.ac.uk/biostudies/studies/S-EPMC9107957biostudies-literatureUnknown16(11)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.ACS chemical biologySimple Esterification of [1-¹³C]-Alpha-Ketoglutarate Enhances Membrane Permeability and Allows for Noninvasive Tracing of Glutamate and Glutamine Production.PMC9107957R00 CA222493K99 CA222493R00CA222493Blackman BYamamoto KSwenson REMiura NBrender JRKrishna MCAbuSalim JEMushti CCamphausen KASeki TKesarwala AHfalseSimple Esterification of [1-¹³C]-Alpha-Ketoglutarate Enhances Membrane Permeability and Allows for Noninvasive Tracing of Glutamate and Glutamine Production.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.2021-01-01T00:00:00Z2021 Nov2025-04-25T23:40:19.264Z2025-04-06T09:24:50.51ZS-EPMC91079573455472410.1021/acschembio.1c00561