Rapid Catalyst Capture Enables Metal-Free para-Hydrogen-Based Hyperpolarized Contrast Agents

Abstract

Hyperpolarization techniques based on the use of para-hydrogen provide orders of magnitude signal enhancement for magnetic resonance spectroscopy and imaging. The main drawback limiting widespread applicability of para-hydrogen-based techniques in biomedicine is the presence of organometallic compounds (the polarization transfer catalysts) in solution with hyperpolarized contrast agents. These catalysts are typically complexes of platinum-group metals, and their administration in vivo should be avoided. Herein, we show how extraction of a hyperpolarized compound from an organic phase to an aqueous phase combined with a rapid (less than 10 s) Ir-based catalyst capture by metal scavenging agents can produce pure para-hydrogen-based hyperpolarized contrast agents, as demonstrated by high-resolution nuclear magnetic resonance (NMR) spectroscopy and inductively coupled plasma atomic emission spectroscopy (ICP-AES). The presented methodology enables fast and efficient means of producing pure hyperpolarized aqueous solutions for biomedical and other uses.

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

“…[23,34] Additionally,s ignificantly longer hyperpolarization lifetimes may be achievable in doubly labelled acetate through population of 13 C- 13 Cs inglet states, [33] which very recently have been shown to extend the lifetime of HP 1,2-13 C-pyruvate. [28] In principle,s uch states are more easily populated via SABRE than d-DNP.S uch improvements, combined with recent demonstrations of SABRE under aqueous [34] and heterogeneous catalytic conditions, [35] as well as novel catalyst-filtration/separation methods, [24,36] bode well for ultimate translation of SABRE-based approaches for avariety of promising biological and biomedical applications.…”

Catalyst‐Substrate Effects on Biocompatible SABRE Hyperpolarization

“…If a nominal, 1 g dosage of the contrast agent is used, this equates to a maximum 10 ppm iridium concentration in a single bolus. A number of methods for depleting the iridium content in solution have been reported, including bi‐phasic catalysis, ion‐exchange chromatography and solid phase scavengers …”

Multiple Quantum Coherences Hyperpolarized at Ultra‐Low Fields

“…SABRE at high magnetic field for high-resolution NMR encounters difficulties due to magnetic field inhomogeneity caused by pH 2 bubbling; [38] this is not a problem for ultra-low field (ULF) NMR and even allows continuous SABRE, [39] radiowave amplification by stimulated emission of radiation (RASER) [13] and QUASi-Resonance SABRE (QUASR). [41][42][43][44][45][46] When it comes to biomedical applications, usually, it is the goal to populate one dedicated spin state and, as a result, boost the MRI signal of the targeted nuclei. [41][42][43][44][45][46] When it comes to biomedical applications, usually, it is the goal to populate one dedicated spin state and, as a result, boost the MRI signal of the targeted nuclei.…”