The 13C hyperpolarized pyruvate generated by ParaHydrogen detects the response of the heart to altered metabolism in real time

Abstract

Many imaging methods have been proposed to act as surrogate markers of organ damage, yet for many candidates the essential biomarkers characteristics of the injured organ have not yet been described. Hyperpolarized [1-13C]pyruvate allows real time monitoring of metabolism in vivo. ParaHydrogen Induced Polarization (PHIP) is a portable, cost effective technique able to generate 13C MR hyperpolarized molecules within seconds. The introduction of the Side Arm Hydrogenation (SAH) strategy offered a way to widen the field of PHIP generated systems and to make this approach competitive with the currently applied dissolution-DNP (Dynamic Nuclear Polarization) method. Herein, we describe the first in vivo metabolic imaging study using the PHIP-SAH hyperpolarized [1-13C]pyruvate. In vivo maps of pyruvate and of its metabolic product lactate have been acquired on a 1 T MRI scanner. By comparing pyruvate/lactate 13C label exchange rate in a mouse model of dilated cardiomyopathy, it has been found that the metabolic dysfunction occurring in the cardiac muscle of the diseased mice can be detected well before the disease can be assessed by echocardiographic investigations.

High-Resolution Nuclear Magnetic Resonance Spectroscopy with Picomole Sensitivity by Hyperpolarization on a Chip

“…The substrate 2 was chosen in view of future studies based on side-arm hydrogenation. 31,32,41 The chip consists of three laser-cut layers of poly methylmethacrylate (PMMA) bonded together, as shown in Fig. 2b.…”

Metabolic Studies of Tumor Cells Using [1‐13C] Pyruvate Hyperpolarized by Means of PHIP‐Side Arm Hydrogenation

“…To further improve the biological compatibility of the administered pyruvate solution, ethanol has been completely deleted from the hydrogenation step. In previous works, few microliters of ethanol were added, as hydrogenation co‐solvent, to the organic solution (chloroform). Actually, the use of ethanol was pursued in order to replace the less‐biologically compatible methanol that is the commonly used with this type of hydrogenation catalysts.…”

“Direct” 13C Hyperpolarization of 13C‐Acetate by MicroTesla NMR Signal Amplification by Reversible Exchange (SABRE)

“…Recently, PHIP was used to create hyperpolarized esters that, when base‐hydrolyzed, can rapidly produce HP carboxylic acid derivatives including 13 C‐acetate. HP 13 C‐pyruvate created via PHIP and hydrolysis has been recently used for detection of altered heart metabolism in vivo . Taken together, the above developments indicate that MRI of HP biomolecules may embody a game‐changing technology for minimally invasive molecular imaging of metabolism without the use of ionizing radiation …”