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Hyperpolarized [6- 13 C, 15 N 3 ]-Arginine as a Probe for in vivo Arginase Activity.
ACS Chemical Biology 2019 March 21
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. 13 C-enriched arginine can be used as a hyperpolarized (HP) magnetic resonance (MR) probe for arginase flux since the arginine carbon-6 resonance (157ppm) is converted to urea (163ppm) following arginase-catalyzed hydrolysis. However, scalar relaxation from adjacent 14 N-nuclei shortens cabon-6 T1 and T2 times, yielding poor spectral properties. To address these limitations, we report the synthesis of [6-13 C,15 N3 ]-arginine and demonstrate that 15 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 [6-13 C,15 N3 ]-arginine as a non-invasive arginase imaging agent for preclinical studies, with the potential for future clinical diagnostic use.
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