In this presentation, the latest developments towards imaging applications of parahydrogen-based hyperpolarisation methods will be discussed. Recent advances of both the hydrogenative parahydrogen-induced polarisation (PHIP) and non-hydrogenative signal amplification by reversible exchange (SABRE) methods will be explored. In particular the talk will focus on developments in key aspects of clinical relevance including the optimisation of hyperpolarisation levels and lifetimes, strategies for increasing the range of agents amenable to hyperpolarisation, and developments that will allow for the delivery of biocompatible agents including both the solvent conditions and the removal of the transition metal catalyst.
This presentation will benefit MRI specialists who are interested in learning more about the emerging parahydrogen-based techniques for the generation of hyperpolarised contrast agents. In particular, this talk will be of interest to those wanting to understand the opportunities presented by these methods and the recent progress that has been made towards MRI applications.
The development of hyperpolarised metabolic imaging agents is a topic of significant interest within the MRI community due to the potential for applications in clinical diagnosis. Parahydrogen (p-H2) based methods, which were first introduced in the late 1980's, can be used to generate hyperpolarised agents with high levels of polarisation (>10%) in relatively short time periods (seconds to minutes). [1-2] Key advantages of this hyperpolarisation approach are that the source of hyperpolarisation, the singlet nuclear spin isomer of H2 (p-H2), is relatively easy to generate and can be stored and transported to the point of use. In addition, the polarisation step does not require either strong magnetic fields or cryogens. Therefore parahydrogen hyperpolarisation has the potential to provide a cheaper and faster route to hyperpolarised agents for MRI applications. However, as this is a relatively new technology, many challenges need to be overcome in order to enable practical MRI applications.
In this presentation, the latest developments towards imaging applications of parahydrogen hyperpolarisation methods will be discussed. In the first part of the talk, the focus will be on the parahydrogen induced polarisation (PHIP) approach, which generates the hyperpolarised agent by reacting a carefully chosen chemical precursor with p-H2 in order to form a hyperpolarised product molecule that contains the two hydrogen nuclei from p-H2. The resultant hyperpolarisation can be detected either on the 1H nuclei or following transfer to another nucleus such as 13C. This is the so-called hydrogenative approach to parahydrogen hyperpolarisation. Demonstrations of in vivo MRI using agents hyperpolarised by PHIP [3-4] will be discussed along with a synthetic route to hyperpolarising 13C-labelled metabolites, such as pyruvate, using the side-arm-hydrogenation (SAH) PHIP approach. [5]
In the second part of the talk, the focus will be on the non-hydrogenative form of PHIP that is called signal amplification by reversible exchange (SABRE). [6,7] The SABRE approach catalytically transfers p-H2-derived polarisation to the target molecule using a reversible exchange reaction that does not change the chemical identity of the hyperpolarised agent. This method is rapid, with polarisation build-up over a period of only a few seconds, and is fully reversible. As a result, a single sample can be re-polarised multiple times. Here the focus will be on recent developments that bring the method closer to the goal of developing SABRE hyperpolarised agents for in vivo imaging. In particular the following aspects will be explored.
1. Bowers and Weitekamp, J. Amer. Chem. Soc. 109 (1987) 5541-5542.
2. Green et al. Prog. Nucl. Magn. Reson. Spectrosc. 67 (2012) 1-48.
3. Olsson et al. Magn. Reson. Med. 55 (2006) 731-737.
4. Coffey et al. Anal. Chem. 88 (2016) 8279-8288.
5. Raineri et al. Angew. Chemie 50 (2011) 7350-7353.
6. Adams et al. Science 323 (2009) 1708.
7. Rayner and Duckett, Angew. Chemie 57 (2018) 6742-6753.