Acute porcine renal metabolic effect of endogastric soft drink administration assessed with hyperpolarized [1‐13c]pyruvate

Abstract

PurposeOur aim was to determine the quantitative reproducibility of metabolic breakdown products in the kidney following intravenous injection of hyperpolarized [1‐13C]pyruvate and secondly to investigate the metabolic effect on the pyruvate metabolism of oral sucrose load using dissolution dynamic nuclear polarization. By this technique, metabolic alterations in several different metabolic related diseases and their metabolic treatment responses can be accessed.MethodsIn four healthy pigs the lactate‐to‐pyruvate, alanine‐to‐pyruvate and bicarbonate‐to‐pyruvate ratio was measured following administration of regular cola and consecutive injections of hyperpolarized [1‐13C]pyruvate four times within an hour.ResultsThe overall lactate‐to‐pyruvate metabolic profile changed significantly over one hour following an acute sucrose load leading to a significant rise in blood glucose.ConclusionThe reproducibility of hyperpolarized magnetic resonance spectroscopy in the healthy pig kidney demonstrated a repeatability of more than 94% for all metabolites and, furthermore, that the pyruvate to lactate conversion and the blood glucose level is elevated following endogastric sucrose administration. Magn Reson Med 74:558–563, 2015. © 2015 The Authors Magnetic Resonance in Medicine published by Wiley Periodicals, Inc. on behalf of International Society for Magnetic Resonance in Medicine. This is an open access article under the terms of the Creative Commons Attribution‐NonCommercial‐NoDerivs License, which permits use and distribution in any medium, provided the original work is properly cited, the use is non‐commercial and no modifications or adaptations are made.

Fumarase activity: an in vivo and in vitro biomarker for acute kidney injury

“…In principle any small molecular probe can be hyperpolarized as long as they contain a nuclear spin, typically 13 C2021. Currently there is an large array of commercial available hyperpolarized of 13 C-labeled molecules which have been utilized in many different animal models of cancer2223, myocardial ischemia242526 and renal diseases27282930, and more recently in patients and healthy volunteers3132 Additionally, [1,4- 13 C]fumarate has been shown to be a reliable imaging biomarker for monitoring cellular necrosis33 in a rat model of xenograft tumors and subsequently in a rat model with folic acid-induced AKI34. These previous results showed an increased 13 C-malate signal in kidneys with progressive tubular necrosis.…”

The use of hyperpolarized carbon-13 magnetic resonance for molecular imaging

“…Generally it can polarize up to ~200 μL of sample, limiting its use to studies in small animals. More recently, a larger commercially-available polarizer—SpinLab (General Electric)—was developed with a much greater throughput (4 simultaneous samples of volume greater than 1mL), enabling HP imaging in large animals and humans [103,104]. …”

“…In hyperpolarized imaging, this necessitates the use of a low flip-angle which carries a significant signal-to-noise penalty. However, due to its simplicity and availability on most clinical and preclinical MR scanners, single-point CSI sequence is still a popular pulse sequence (figure B) [104]. Furthermore, its simplicity makes CSI relatively immune to artifacts; thus, even if higher resolutions or faster acquisitions can be achieved using other methods, single-point CSI can yield well-understood reference images for validation.…”

“…As such, the observed signal reflects the endogenous lactate pool size and the redox state of the system. Many external perturbations or pathologies change the lactate pool, thereby allowing HP pyruvate to be used as a biomarker in many different pathologies, including acute injury, inflammation, or cancer [104,124,171,172]. …”

“…An in vivo rat study demonstrated significant conversion of HP pyruvate to both HP lactate and HP bicarbonate in the kidneys, while there was minimal conversion to alanine [259]. In another study, when pigs were given an oral sucrose load, it was found that the lactate to pyruvate ratio correlated with the blood glucose level, while all other metabolites of pyruvate remained unchanged [104]. …”