Labile photo-induced free radical in alpha-ketoglutaric acid: a universal endogenous polarizing agent for in vivo hyperpolarized 13C magnetic resonance.

Hyperpolarized (HP) 13 C magnetic resonance enables non-invasive probing of metabolism in vivo. To date, only 13 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 13 C-molecules such as [1- 13 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 13 C relaxation time in frozen HP 13 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- 13 C]lactate.