Trehalose as an alternative to glycerol as a glassing agent for in vivo DNP MRI

In dynamic nuclear polarization (DNP), the solutions of the hyperpolarizable molecule and the paramagnetic agent need to form a glass when frozen to attain significant levels of polarization in reasonable time periods. Molecules which do not form glasses by themselves are often mixed with excipients to form glasses. While glassing agents are often essential in DNP studies, they have the potential to perturb the metabolic measurements that are being studied. Glycerol, the glassing agent of choice for in vivo DNP studies, is effective at reducing ice crystal formation during freezing but is rapidly metabolized, potentially altering the redox and ATP balance of the system. As a biologically inert alternative to glycerol, we show here that 15–20 wt % trehalose yields a glass that polarizes samples more rapidly than the commonly used 60% wt formulation of glycerol and yields similar polarization levels within clinically relevant timeframes. Trehalose may be an attractive alternative to glycerol for situations where there may be concerns about glycerol’s glucogenic potential and possible alteration of the ATP/ADP and redox balance.