Labile Photo-Induced Free Radical in α-Ketoglutaric Acid: a Universal Endogenous Polarizing Agent for In Vivo Hyperpolarized C Magnetic Resonance.

Hyperpolarized (HP) C magnetic resonance enables non-invasive probing of metabolism in vivo. To date, only C-molecules hyperpolarized with persistent trityl radicals have been injected in humans. We show here that the free radical photo-induced in alpha-ketoglutaric acid (α-KG) can be used to hyperpolarize photo-inactive C-molecules such as [1-C]lactate. α-KG is an endogenous molecule with an exceptionally high radical yield under photo-irradiation, up to 50 %, and its breakdown product, succinic acid, is also endogenous. This radical precursor therefore exhibits an excellent safety profile for translation to human studies. The labile nature of the radical means that no filtration is required prior to injection while also offering the opportunity to extend the C relaxation time in frozen HP C-molecules for storage and transport. The potential for in vivo metabolic studies is demonstrated in the rat liver following the injection of a physiological dose of HP [1-C]lactate.