2021年7月
Synthesis of [1-13C-5-12C]-alpha-ketoglutarate enables noninvasive detection of 2-hydroxyglutarate
NMR in Biomedicine
- 巻
- e4588
- 号
- 開始ページ
- e4588
- 終了ページ
- 記述言語
- 英語
- 掲載種別
- 研究論文(学術雑誌)
- DOI
- 10.1002/nbm.4588
- 出版者・発行元
- Wiley Analytical Science
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-13C-MRS) using [1-13C]-α-KG as a probe, but peak contamination from naturally occurring [5-13C]-α-KG overlaps with the [1-13C]-2-HG peak. Via a newly developed oxidative-Stetter reaction, [1-13C-5-12C]-α-KG was synthesized. α-KG metabolism was measured via HP-13C-MRS using [1-13C-5-12C]-α-KG as a probe. [1-13C-5-12C]-α-KG was synthesized in high yields, and successfully eliminated the signal from C5 of α-KG in the HP-13C-MRS spectra. In HCT116 IDH1 R132H cells, [1-13C-5-12C]-α-KG allowed for unimpeded detection of [1-13C]-2-HG. 12C-enrichment represents a novel method to circumvent spectral overlap, and [1-13C-5-12C]-α-KG shows promise as a probe to study IDH1 mutant tumors and α-KG metabolism.
- ID情報
-
- DOI : 10.1002/nbm.4588
- PubMed ID : 34263489