Hyperpolarized [6-13C,15N3]-Arginine as a Probe for in Vivo Arginase Activity
| Autor: | Roozbeh Eskandari, Kayvan R. Keshari, Kristin L. Granlund, Andrew Cho |
|---|---|
| Rok vydání: | 2019 |
| Předmět: |
0301 basic medicine
chemistry.chemical_classification medicine.diagnostic_test Arginine 010405 organic chemistry Chemistry Magnetic resonance imaging General Medicine 01 natural sciences Biochemistry Imaging agent In vitro 0104 chemical sciences Arginase 03 medical and health sciences 030104 developmental biology Enzyme In vivo medicine Biophysics Molecular Medicine Flux (metabolism) |
| Zdroj: | ACS Chemical Biology. 14:665-673 |
| ISSN: | 1554-8937 1554-8929 |
| DOI: | 10.1021/acschembio.8b01044 |
| Popis: | 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 T 1 and T 2 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. |
| Databáze: | OpenAIRE |
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