Hyperpolarized [6-13C,15N3]-Arginine as a Probe for in Vivo Arginase Activity

Andrew Cho, Roozbeh Eskandari, Kristin L. Granlund, Kayvan R. Keshari

Research output: Contribution to journalArticlepeer-review

6 Scopus citations

Abstract

Alterations in arginase enzyme expression are linked with various diseases and have been shown to support disease progression, thus motivating the development of an imaging probe for this enzymatic target. 13C-enriched arginine can be used as a hyperpolarized (HP) magnetic resonance (MR) probe for arginase flux since the arginine carbon-6 resonance (157 ppm) is converted to urea (163 ppm) following arginase-catalyzed hydrolysis. However, scalar relaxation from adjacent 14N-nuclei shortens cabon-6 T1 and T2 times, yielding poor spectral properties. To address these limitations, we report the synthesis of [6-13C,15N3]-arginine and demonstrate that 15N-enrichment increases carbon-6 relaxation times, thereby improving signal-to-noise ratio and spectral resolution. By overcoming these limitations with this novel isotope-labeling scheme, we were able to perform in vitro and in vivo arginase activity measurements with HP MR. We present HP [6-13C,15N3]-arginine as a noninvasive arginase imaging agent for preclinical studies, with the potential for future clinical diagnostic use.

Original languageEnglish (US)
Pages (from-to)665-673
Number of pages9
JournalACS Chemical Biology
Volume14
Issue number4
DOIs
StatePublished - Apr 19 2019
Externally publishedYes

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Medicine

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