Real-Time insight into in vivo redox status utilizing hyperpolarized [1-13C] N-acetyl cysteine

Abstract Drastic sensitivity enhancement of dynamic nuclear polarization is becoming an increasingly critical methodology to monitor real-time metabolic and physiological information in chemistry, biochemistry, and biomedicine. However, the limited number of available hyperpolarized 13C probes, whic...

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Autores principales:	Kazutoshi Yamamoto, Ana Opina, Deepak Sail, Burchelle Blackman, Keita Saito, Jeffrey R. Brender, Ronja M. Malinowski, Tomohiro Seki, Nobu Oshima, Daniel R. Crooks, Shun Kishimoto, Yu Saida, Yasunori Otowa, Peter L. Choyke, Jan H. Ardenkjær-Larsen, James B. Mitchell, W. Marston Linehan, Rolf E. Swenson, Murali C. Krishna
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2021
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/bad8b5268826453db750b84fe20d286f
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spelling	oai:doaj.org-article:bad8b5268826453db750b84fe20d286f2021-12-02T17:48:00ZReal-Time insight into in vivo redox status utilizing hyperpolarized [1-13C] N-acetyl cysteine10.1038/s41598-021-90921-02045-2322https://doaj.org/article/bad8b5268826453db750b84fe20d286f2021-06-01T00:00:00Zhttps://doi.org/10.1038/s41598-021-90921-0https://doaj.org/toc/2045-2322Abstract Drastic sensitivity enhancement of dynamic nuclear polarization is becoming an increasingly critical methodology to monitor real-time metabolic and physiological information in chemistry, biochemistry, and biomedicine. However, the limited number of available hyperpolarized 13C probes, which can effectively interrogate crucial metabolic activities, remains one of the major bottlenecks in this growing field. Here, we demonstrate [1-13C] N-acetyl cysteine (NAC) as a novel probe for hyperpolarized 13C MRI to monitor glutathione redox chemistry, which plays a central part of metabolic chemistry and strongly influences various therapies. NAC forms a disulfide bond in the presence of reduced glutathione, which generates a spectroscopically detectable product that is separated from the main peak by a 1.5 ppm shift. In vivo hyperpolarized MRI in mice revealed that NAC was broadly distributed throughout the body including the brain. Its biochemical transformation in two human pancreatic tumor cells in vitro and as xenografts differed depending on the individual cellular biochemical profile and microenvironment in vivo. Hyperpolarized NAC can be a promising non-invasive biomarker to monitor in vivo redox status and can be potentially translatable to clinical diagnosis.Kazutoshi YamamotoAna OpinaDeepak SailBurchelle BlackmanKeita SaitoJeffrey R. BrenderRonja M. MalinowskiTomohiro SekiNobu OshimaDaniel R. CrooksShun KishimotoYu SaidaYasunori OtowaPeter L. ChoykeJan H. Ardenkjær-LarsenJames B. MitchellW. Marston LinehanRolf E. SwensonMurali C. KrishnaNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 11, Iss 1, Pp 1-9 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Kazutoshi Yamamoto Ana Opina Deepak Sail Burchelle Blackman Keita Saito Jeffrey R. Brender Ronja M. Malinowski Tomohiro Seki Nobu Oshima Daniel R. Crooks Shun Kishimoto Yu Saida Yasunori Otowa Peter L. Choyke Jan H. Ardenkjær-Larsen James B. Mitchell W. Marston Linehan Rolf E. Swenson Murali C. Krishna Real-Time insight into in vivo redox status utilizing hyperpolarized [1-13C] N-acetyl cysteine
description	Abstract Drastic sensitivity enhancement of dynamic nuclear polarization is becoming an increasingly critical methodology to monitor real-time metabolic and physiological information in chemistry, biochemistry, and biomedicine. However, the limited number of available hyperpolarized 13C probes, which can effectively interrogate crucial metabolic activities, remains one of the major bottlenecks in this growing field. Here, we demonstrate [1-13C] N-acetyl cysteine (NAC) as a novel probe for hyperpolarized 13C MRI to monitor glutathione redox chemistry, which plays a central part of metabolic chemistry and strongly influences various therapies. NAC forms a disulfide bond in the presence of reduced glutathione, which generates a spectroscopically detectable product that is separated from the main peak by a 1.5 ppm shift. In vivo hyperpolarized MRI in mice revealed that NAC was broadly distributed throughout the body including the brain. Its biochemical transformation in two human pancreatic tumor cells in vitro and as xenografts differed depending on the individual cellular biochemical profile and microenvironment in vivo. Hyperpolarized NAC can be a promising non-invasive biomarker to monitor in vivo redox status and can be potentially translatable to clinical diagnosis.
format	article
author	Kazutoshi Yamamoto Ana Opina Deepak Sail Burchelle Blackman Keita Saito Jeffrey R. Brender Ronja M. Malinowski Tomohiro Seki Nobu Oshima Daniel R. Crooks Shun Kishimoto Yu Saida Yasunori Otowa Peter L. Choyke Jan H. Ardenkjær-Larsen James B. Mitchell W. Marston Linehan Rolf E. Swenson Murali C. Krishna
author_facet	Kazutoshi Yamamoto Ana Opina Deepak Sail Burchelle Blackman Keita Saito Jeffrey R. Brender Ronja M. Malinowski Tomohiro Seki Nobu Oshima Daniel R. Crooks Shun Kishimoto Yu Saida Yasunori Otowa Peter L. Choyke Jan H. Ardenkjær-Larsen James B. Mitchell W. Marston Linehan Rolf E. Swenson Murali C. Krishna
author_sort	Kazutoshi Yamamoto
title	Real-Time insight into in vivo redox status utilizing hyperpolarized [1-13C] N-acetyl cysteine
title_short	Real-Time insight into in vivo redox status utilizing hyperpolarized [1-13C] N-acetyl cysteine
title_full	Real-Time insight into in vivo redox status utilizing hyperpolarized [1-13C] N-acetyl cysteine
title_fullStr	Real-Time insight into in vivo redox status utilizing hyperpolarized [1-13C] N-acetyl cysteine
title_full_unstemmed	Real-Time insight into in vivo redox status utilizing hyperpolarized [1-13C] N-acetyl cysteine
title_sort	real-time insight into in vivo redox status utilizing hyperpolarized [1-13c] n-acetyl cysteine
publisher	Nature Portfolio
publishDate	2021
url	https://doaj.org/article/bad8b5268826453db750b84fe20d286f
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Real-Time insight into in vivo redox status utilizing hyperpolarized [1-13C] N-acetyl cysteine

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