TY - JOUR
T1 - Hyperpolarized [6-13C,15N3]-Arginine as a Probe for in Vivo Arginase Activity
AU - Cho, Andrew
AU - Eskandari, Roozbeh
AU - Granlund, Kristin L.
AU - Keshari, Kayvan R.
N1 - Funding Information:
We would like to thank G. Sukenick and the Memorial Sloan Kettering Nuclear Magnetic Resonance Core for helpful advice with NMR experiments and high-resolution mass spectrometry measurements. This work was supported by the National Institutes of Health, F30 CA225174 (A.C.), T32 GM007739 (A.C. and K.R.K.), and P30 CA008748 (K.R.K.), the Tow Foundation Postdoctoral Fellowship (R.E.), the Ludwig Center for Basic and Translational Immunology (K.R.K.), Geoffrey Beene Cancer Research Center (K.R.K.), and the Thompson Family Foundation (K.R.K.).
Funding Information:
This work was supported by the National Institutes of Health, F30 CA225174 (A.C.), T32 GM007739 (A.C. and K.R.K.), and P30 CA008748 (K.R.K.), the Tow Foundation Postdoctoral Fellowship (R.E.), the Ludwig Center for Basic and Translational Immunology (K.R.K.), Geoffrey Beene Cancer Research Center (K.R.K.), and the Thompson Family Foundation (K.R.K.).
Publisher Copyright:
© 2019 American Chemical Society.
PY - 2019/4/19
Y1 - 2019/4/19
N2 - 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.
AB - 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.
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U2 - 10.1021/acschembio.8b01044
DO - 10.1021/acschembio.8b01044
M3 - Article
C2 - 30893552
AN - SCOPUS:85064847664
SN - 1554-8929
VL - 14
SP - 665
EP - 673
JO - ACS Chemical Biology
JF - ACS Chemical Biology
IS - 4
ER -