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Labile Photo-Induced Free Radical in α-Ketoglutaric Acid: a Universal Endogenous Polarizing Agent for In Vivo Hyperpolarized 13C Magnetic Resonance.

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Gaunt, Adam P 
Lewis, Jennifer S 
Hesse, Friederike 
Cheng, Tian 
Marco-Rius, Irene 


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.



dynamic nuclear polarization, imaging agents, keto acids, metabolism, photochemistry

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Angew Chem Weinheim Bergstr Ger

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Cancer Research UK (CB4100)
Cancer Research UK (C14303/A17197)
European Commission Horizon 2020 (H2020) ERC (963998)
European Research Council (682574)