HET-SABRE MRI Catalyst

Heterogenous Water-Compatible and Removable Catalyst for Nuclear Magnetic Resonance (NMR) Signal Amplification by Reversible Exchange

At a Glance

Researchers at Colorado State University have developed a novel catalyst for nuclear magnetic resonance (NMR). This catalyst is water-compatible, and easily removed from the sample and recycled. The experimental results of the HET-SABRE catalyst successfully amplified the NMR signal through hyperpolarization on pyridine in water, and open the possibility of applying SABRE for high sensitivity MRI imaging and medical advancements.

Background

Magnetic resonance imaging (MRI) is the gold standard diagnostic tool in medicine. However, nuclear magnetic resonance (NMR), the phenomenon underlying MRI, is fundamentally low in sensitivity and MRI often misses small anomalies, such as early-stage tumors. Therefore, there are tremendous efforts to improve MRI sensitivity for earlier diagnosis of life-threatening diseases in the medical imaging field.

Hyperpolarization is a technique where the NMR signal is amplified up to several orders of magnitude by manipulating the relative distribution of nuclear spin states. Currently, the state of the art is to use dynamic nuclear polarization (DNP) to create hyperpolarization. In DNP, the targeted compound is mixed with a free radical, cooled to an extremely low temperature, and irradiated with microwaves to create hyperpolarization. This is a time and resource intensive process, requiring a quick thaw of the sample and limited field of view.

In contrast, signal amplification by reversible exchange (SABRE) is being studied to enhance imaging capabilities and create a more stable molecule for higher sensitivity in MRI. In SABRE applications, an organometallic catalyst transfers hyperpolarization from hydrogen gas in the para spins state to the sample. This does not require such low temperatures, and creates a larger hyperpolarization. However, previous SABRE catalysts were limited in medical applications because (1) the catalysts are not active in water, (2) they cannot be easily removed from the sample, and (3) the homogenous catalyst presents a toxic organometallic catalyst in solution after the polarization is achieved, limiting its use in biomedical applications.

Overview

The catalyst developed herein is a new type of heterogeneous SABRE (HET-SABRE) catalyst that is both water compatible and easily removed and recycled from the sample. It can be introduced to biological samples in aqueous solution, and is a solid state so it is easily removed from the sample after transferring hyperpolarization. The HET-SABRE catalyst produces a much higher polarization, similar to that of a homogenous catalyst in methanol, and amplification was still possible in water. Furthermore, it does not require post-synthesis modification. The HET-SABRE catalyst also allows for real time imaging, and allows for much greater sensitivity due to the stability of the catalyst.

Figure 1, below, demonstrates the NMR spectrum of the HET-SABRE catalyst. Importantly, the hyperpolarization in the substrate is high, similar to that of a homogenous catalyst, and in the 50-fold range. This is much stronger polarization than other HET-SABRE catalysts, while keeping the solution colorless and transparent due to strong binding.

Figure 2, below, shows the efficiency of the reused catalyst, in multiple experiments the catalyst shows amplification, demonstrating for the first time the recyclability of a SABRE catalyst.

Benefits

  • Produces high polarization, 50-100 fold enhancement
  • Range of amplification in both methanol and water demonstrated
  • Biocompatible SABRE process
  • Separates easily from sample due to solid state
  • Recyclable catalyst with demonstrated sensitivity
  • Ease of production and minimal equipment needed to produce contrast agent
  • Catalyst does not produce organometallic catalyst in solution
  • Suitable for biomedical applications
  • Enhancement of sensitivity in imaging

Applications

  • Biomedical applications
  • MRI
    • Disease diagnosis
    • Early tumor detection
    • Small scale and/or detailed imaging

Publications

Min, et al. 2023 “Water-compatible and recyclable heterogeneous SABRE catalyst for NRM signal amplification. JACS Au https://doi.org/10.1021/jacsau.3c00487

Last Updated: November 2023
Graphic showing HET-SABRE MRI Catalyst
Opportunity

Available for Licensing
TRL: 4

IP Status

US Provisional Patent

Inventors

Jean Chung
Keunhong Jeong
Sein Min

Reference Number
2022-050
Licensing Manager

Aly Hoeher
Aly.Hoeher@colostate.edu
970-491-7100