Stable electron-irradiated [1-$^{13}$C]alanine radicals for clinically viable metabolic imaging with Dynamic Nuclear Polarization

Abstract

Dissolution Dynamic Nuclear Polarisation (dDNP) increases the sensitivity of magnetic resonance experiments by $>10^4$-fold, permitting isotopically-labelled molecules to be transiently visible in MRI scans. dDNP requires a source of unpaired electrons in contact with labelled nuclei, cooled to $\sim$1K, and spin-pumped into a given state by microwaves. These electrons are usually chemical radicals, requiring removal by filtration prior to injection into humans. Alternative sources, such as UV irradiation, generate lower polarisation and require cryogenic transport. We present ultra-high-dose-rate electron irradiation as a novel alternative for generating non-persistent radicals in alanine/glycerol mixtures. These are stable for months at room temperature, quench spontaneously upon dissolution, are present in dose-dependent concentrations, and generate comparable nuclear polarisation to trityl radicals used clinically (20\%) through a novel mechanism. This process is inherently sterilising, permitting imaging of alanine metabolism \textit{in vivo}. As well as scientific novelty, this overcomes the biggest barrier to clinically translating dDNP.