scholarly journals Real Time Nuclear Magnetic Resonance Detection of Fumarase Activity using Parahydrogen-Hyperpolarized [1-13C]fumarate

Author(s):  
James Eills ◽  
Eleonora Cavallari ◽  
Carla Carrera ◽  
Dmitry Budker ◽  
Silvio Aime ◽  
...  

Hyperpolarized fumarate can be used as a probe of real-time metabolism in vivo, using carbon-13 magnetic resonance imaging. Dissolution dynamic nuclear polarization is commonly used to produce hyperpolarized fumarate, but a cheaper and faster alternative is to produce hyperpolarized fumarate via PHIP (parahydrogen induced polarization). In this work we <i>trans</i>-hydrogenate [1-<sup>13</sup>C]acetylene dicarboxylate with <i>para</i>-enriched hydrogen using a commercially available Ru catalyst in water to produce hyperpolarized [1-<sup>13</sup>C]fumarate. We show that fumarate is produced in 89% yield, with succinate as a side product in 11% yield. The proton polarization is converted into <sup>13</sup>C magnetization using a constant adiabaticity field cycle, and a polarization level of 25% is achieved using 86% <i>para</i>-enriched hydrogen gas. We inject the hyperpolarized [1-<sup>13</sup>C]fumarate into cell suspensions and track the metabolism. This work opens the path to greatly accelerated preclinical studies using fumarate as a biomarker.

2019 ◽  
Author(s):  
James Eills ◽  
Eleonora Cavallari ◽  
Carla Carrera ◽  
Dmitry Budker ◽  
Silvio Aime ◽  
...  

Hyperpolarized fumarate can be used as a probe of real-time metabolism in vivo, using carbon-13 magnetic resonance imaging. Dissolution dynamic nuclear polarization is commonly used to produce hyperpolarized fumarate, but a cheaper and faster alternative is to produce hyperpolarized fumarate via PHIP (parahydrogen induced polarization). In this work we <i>trans</i>-hydrogenate [1-<sup>13</sup>C]acetylene dicarboxylate with <i>para</i>-enriched hydrogen using a commercially available Ru catalyst in water to produce hyperpolarized [1-<sup>13</sup>C]fumarate. We show that fumarate is produced in 89% yield, with succinate as a side product in 11% yield. The proton polarization is converted into <sup>13</sup>C magnetization using a constant adiabaticity field cycle, and a polarization level of 25% is achieved using 86% <i>para</i>-enriched hydrogen gas. We inject the hyperpolarized [1-<sup>13</sup>C]fumarate into cell suspensions and track the metabolism. This work opens the path to greatly accelerated preclinical studies using fumarate as a biomarker.


2009 ◽  
Vol 4 (3) ◽  
pp. 193-201 ◽  
Author(s):  
Oliver T. Bruns ◽  
Harald Ittrich ◽  
Kersten Peldschus ◽  
Michael G. Kaul ◽  
Ulrich I. Tromsdorf ◽  
...  

2016 ◽  
Vol 311 (2) ◽  
pp. L208-L218 ◽  
Author(s):  
Dean O. Kuethe ◽  
Piotr T. Filipczak ◽  
Jeremy M. Hix ◽  
Andrew P. Gigliotti ◽  
Raúl San José Estépar ◽  
...  

Animal models play a critical role in the study of acute respiratory distress syndrome (ARDS) and ventilator-induced lung injury (VILI). One limitation has been the lack of a suitable method for serial assessment of acute lung injury (ALI) in vivo. In this study, we demonstrate the sensitivity of magnetic resonance imaging (MRI) to assess ALI in real time in rat models of VILI. Sprague-Dawley rats were untreated or treated with intratracheal lipopolysaccharide or PBS. After 48 h, animals were mechanically ventilated for up to 15 h to induce VILI. Free induction decay (FID)-projection images were made hourly. Image data were collected continuously for 30 min and divided into 13 phases of the ventilatory cycle to make cinematic images. Interleaved measurements of respiratory mechanics were performed using a flexiVent ventilator. The degree of lung infiltration was quantified in serial images throughout the progression or resolution of VILI. MRI detected VILI significantly earlier (3.8 ± 1.6 h) than it was detected by altered lung mechanics (9.5 ± 3.9 h, P = 0.0156). Animals with VILI had a significant increase in the Index of Infiltration ( P = 0.0027), and early regional lung infiltrates detected by MRI correlated with edema and inflammatory lung injury on histopathology. We were also able to visualize and quantify regression of VILI in real time upon institution of protective mechanical ventilation. Magnetic resonance lung imaging can be utilized to investigate mechanisms underlying the development and propagation of ALI, and to test the therapeutic effects of new treatments and ventilator strategies on the resolution of ALI.


2019 ◽  
Vol 141 (51) ◽  
pp. 20209-20214 ◽  
Author(s):  
James Eills ◽  
Eleonora Cavallari ◽  
Carla Carrera ◽  
Dmitry Budker ◽  
Silvio Aime ◽  
...  

2005 ◽  
Vol 65 (18) ◽  
pp. 8324-8330 ◽  
Author(s):  
Yi Tang ◽  
Minjung Kim ◽  
Daniel Carrasco ◽  
Andrew L. Kung ◽  
Lynda Chin ◽  
...  

2012 ◽  
Vol 302 (12) ◽  
pp. F1658-F1662 ◽  
Author(s):  
Cornelius von Morze ◽  
Robert A. Bok ◽  
Jeff M. Sands ◽  
John Kurhanewicz ◽  
Daniel B. Vigneron

Urea functions as a key osmolyte in the urinary concentrating mechanism of the inner medulla. The urea transporter UT-A1 is upregulated by antidiuretic hormone, facilitating faster equilibration of urea between the lumen and interstitium of the inner medullary collecting duct, resulting in the formation of more highly concentrated urine. New methods in dynamic nuclear polarization, providing ∼50,000-fold enhancement of nuclear magnetic resonance signals in the liquid state, offer a novel means to monitor this process in vivo using magnetic resonance imaging. In this study, we detected significant signal differences in the rat kidney between acute diuretic and antidiuretic states, using dynamic 13C magnetic resonance imaging following a bolus infusion of hyperpolarized [13C]urea. More rapid medullary enhancement was observed under antidiuresis, consistent with known upregulation of UT-A1.


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