SABRE Hyperpolarization with up to 200 bar Parahydrogen in Standard and Quickly Removable Solvents

Abstract

Parahydrogen (p-H2)-based techniques are known to drastically enhance NMR signals but are usually limited by p-H2 supply. This work reports p-H2-based SABRE hyperpolarization at p-H2 pressures of hundreds of bar, far beyond the typical ten bar currently reported in the literature. A recently designed high-pressure setup was utilized to compress p-H2 gas up to 200 bar. The measurements were conducted using a sapphire high-pressure NMR tube and a 43 MHz benchtop NMR spectrometer. In standard methanol solutions, it could be shown that the signal intensities increased with pressure until they eventually reached a plateau. A polarization of about 2%, equal to a molar polarization of 1.2 mmol L−1, could be achieved for the sample with the highest substrate concentration. While the signal plateaued, the H2 solubility increased linearly with pressure from 1 to 200 bar, indicating that p-H2 availability is not the limiting factor in signal enhancement beyond a certain pressure, depending on sample composition. Furthermore, the possibility of using liquefied ethane and compressed CO2 as removable solvents for hyperpolarization was demonstrated. The use of high pressures together with quickly removable organic/non-organic solvents represents an important breakthrough in the field of hyperpolarization, advancing SABRE as a promising tool for materials science, biophysics, and molecular imaging.

In Vivo Metabolic Imaging of [1‐13C]Pyruvate‐d3 Hyperpolarized By Reversible Exchange With Parahydrogen**

“…Once higher volumes are produced, the pyruvate concentration can be increased further by prolonging the evaporation period, as we have shown already (Figure S12). Another approach would be to increase the initial concentration of pyruvate, although to achieve efficient SABRE polarization, the pH 2 concentration in methanol would also need to be increased, for example, by applying higher pressure [24,43] . Therefore, dedicated high‐pressure reactors would need to be developed in the future to enable the desired injection volume and minimize solution losses [44,45] …”

In vivo‐Stoffwechselbildgebung mit [1‐13C]Pyruvat‐d3, hyperpolarisiert durch reversiblen Austausch mit Parawasserstoff**

“…Für das präklinische DNP-Gerät der neuesten Generation wurde ein Variationskoeffizient von 15 % für 13 C-Pyruvat berichtet. [42] Der Ursprung dieser Variabilität ist derzeit spekulativ, aber wir glauben, [24,43] Daher müssten in Zukunft spezielle Hochdruckreaktoren entwickelt werden, um das gewünsch-te Injektionsvolumen zu ermöglichen und die Lösungsverluste zu minimieren. [44,45] Das hier vorgeschlagene Reinigungsverfahren ist schnell und einfach zu installieren und reduziert sowohl Methanol als auch Katalysator unter akut toxische Werte.…”

“…Ein anderer Ansatz wäre die Erhöhung der Anfangskonzentration von Pyruvat, obwohl für eine effiziente SABRE‐Polarisierung auch die pH 2 ‐Konzentration in Methanol erhöht werden müsste, z.B. durch Anwendung eines höheren Drucks [24,43] . Daher müssten in Zukunft spezielle Hochdruckreaktoren entwickelt werden, um das gewünschte Injektionsvolumen zu ermöglichen und die Lösungsverluste zu minimieren [44,45] …”