| Literature DB >> 34263489 |
Natsuko Miura1, Chandrasekhar Mushti2, Deepak Sail2, Jenna E AbuSalim1,3, Kazutoshi Yamamoto4, Jeffrey R Brender4, Tomohiro Seki4, Deyaa I AbuSalim5, Shingo Matsumoto4, Kevin A Camphausen1, Murali C Krishna4, Rolf E Swenson2, Aparna H Kesarwala1,3.
Abstract
Isocitrate dehydrogenase 1 (IDH1) mutations that generate the oncometabolite 2-hydroxyglutarate (2-HG) from α-ketoglutarate (α-KG) have been identified in many types of tumors and are an important prognostic factor in gliomas. 2-HG production can be determined by hyperpolarized carbon-13 magnetic resonance spectroscopy (HP-13 C-MRS) using [1-13 C]-α-KG as a probe, but peak contamination from naturally occurring [5-13 C]-α-KG overlaps with the [1-13 C]-2-HG peak. Via a newly developed oxidative-Stetter reaction, [1-13 C-5-12 C]-α-KG was synthesized. α-KG metabolism was measured via HP-13 C-MRS using [1-13 C-5-12 C]-α-KG as a probe. [1-13 C-5-12 C]-α-KG was synthesized in high yields, and successfully eliminated the signal from C5 of α-KG in the HP-13 C-MRS spectra. In HCT116 IDH1 R132H cells, [1-13 C-5-12 C]-α-KG allowed for unimpeded detection of [1-13 C]-2-HG. 12 C-enrichment represents a novel method to circumvent spectral overlap, and [1-13 C-5-12 C]-α-KG shows promise as a probe to study IDH1 mutant tumors and α-KG metabolism.Entities:
Keywords: 2-hydroxyglutarate; alpha-ketoglutarate; carbon-13 labeled metabolites; hyperpolarized carbon-13 nuclear magnetic resonance spectroscopy; isocitrate dehydrogenase 1
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Year: 2021 PMID： 34263489 PMCID： PMC8492538 DOI： 10.1002/nbm.4588
Source DB: PubMed Journal: NMR Biomed ISSN： 0952-3480 Impact factor: 4.044