Cancer Research UK, Cambridge Institute, University of Cambridge, Robinson Way, Cambridge, CB2 0RE, UK.
General Electric Healthcare, Pollards Wood, Nightingales Lane, Chalfont St Giles, HP8 4SP, UK.
Angew Chem Int Ed Engl. 2022 Jan 10;61(2):e202112982. doi: 10.1002/anie.202112982. Epub 2021 Nov 25.
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.
高极化（HP）13C 磁共振使人们能够在体内对代谢进行非侵入性探测。迄今为止，只有用稳定三苯甲基自由基高极化的 13C 分子被注入人体。我们在此表明，可将在α-酮戊二酸（α-KG）中产生的自由基用于对 [1-13C]乳酸等非光活性 13C 分子进行高极化。α-KG 是一种内源性分子，在光照射下自由基产率极高，可达 50%，其分解产物琥珀酸也是内源性的。因此，这种自由基前体具有极好的安全性，有望转化为人体研究。该自由基的不稳定性意味着在注射前不需要过滤，同时还为在冷冻 HP 13C 分子中延长 13C 弛豫时间以进行储存和运输提供了机会。在注射生理剂量的 HP [1-13C]乳酸后，在大鼠肝脏中证明了体内代谢研究的潜力。
