Hyperpolarized (HP) 13C magnetic resonance enables non-invasive probing of metabolism in vivo. To date, only 13C-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 13C-molecules such as [1-13C]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 13C relaxation time in frozen HP 13C-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 [1-13C]lactate.
α‐Ketoglutaric acid (α‐KG) has an exceptionally high free radical yield under photo‐irradiation at cryogenic temperature. This radical can be used as a universal polarizing agent to hyperpolarize 13C‐molecules such as [1‐13C]lactate, a promising alternative to pyruvate for in vivo metabolic studies by 13C magnetic resonance.
Keywords: dynamic nuclear polarization; imaging agents; keto acids; metabolism; photochemistry.
© 2021 The Authors. Angewandte Chemie published by Wiley-VCH GmbH.