Hyperpolarized [6-(13)C,(15)N(3)]-arginine as a probe for in vivo arginase activity Journal Article
| Authors: | Cho, A.; Eskandari, R.; Granlund, K. L.; Keshari, K. R. |
| Article Title: | Hyperpolarized [6-(13)C,(15)N(3)]-arginine as a probe for in vivo arginase activity |
| 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. 13 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 14 N-nuclei shortens cabon-6 T 1 and T 2 times, yielding poor spectral properties. To address these limitations, we report the synthesis of [6- 13 C, 15 N 3 ]-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 N 3 ]-arginine as a noninvasive arginase imaging agent for preclinical studies, with the potential for future clinical diagnostic use. © 2019 American Chemical Society. |
| Journal Title: | ACS Chemical Biology |
| Volume: | 14 |
| Issue: | 4 |
| ISSN: | 1554-8929 |
| Publisher: | American Chemical Society |
| Date Published: | 2019-04-19 |
| Start Page: | 665 |
| End Page: | 673 |
| Language: | English |
| DOI: | 10.1021/acschembio.8b01044 |
| PUBMED: | 30893552 |
| PROVIDER: | scopus |
| PMCID: | PMC6474818 |
| DOI/URL: | |
| Notes: | Article -- Export Date: 3 June 2019 -- Source: Scopus |
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