Title | Hyperpolarized [6-C,N]-Arginine as a Probe for in Vivo Arginase Activity. |
Publication Type | Journal Article |
Year of Publication | 2019 |
Authors | Cho A, Eskandari R, Granlund KL, Keshari KR |
Journal | ACS Chem Biol |
Volume | 14 |
Issue | 4 |
Pagination | 665-673 |
Date Published | 2019 04 19 |
ISSN | 1554-8937 |
Keywords | Arginase, Arginine, Carbon Isotopes, Kinetics, Molecular Probes, Nitrogen Isotopes |
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. C-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 N-nuclei shortens cabon-6 T and T times, yielding poor spectral properties. To address these limitations, we report the synthesis of [6-C,N]-arginine and demonstrate that N-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-C,N]-arginine as a noninvasive arginase imaging agent for preclinical studies, with the potential for future clinical diagnostic use. |
DOI | 10.1021/acschembio.8b01044 |
Alternate Journal | ACS Chem. Biol. |
PubMed ID | 30893552 |
PubMed Central ID | PMC6474818 |
Grant List | F30 CA225174 / CA / NCI NIH HHS / United States P30 CA008748 / CA / NCI NIH HHS / United States T32 GM007739 / GM / NIGMS NIH HHS / United States |
Submitted by api_import on December 23, 2019 - 10:21am