UV-Irradiated 2-Keto-(1-C-13)Isocaproic Acid for High-Performance C-13 Hyperpolarized MR
Enhancing the sensitivity of magnetic resonance spectroscopy/imaging (MRS/MRI) by dissolution dynamic nuclear polarization (dDNP) has expanded the scope of MRS applications to new fields of research. Most importantly, it has paved the way toward noninvasive studies of the fate of a metabolite in real time. As its name implies, in a typical dDNP experiment, the hyperpolarized (HP) sample is extracted from the polarizer in the liquid state. This procedure limits the HP signal exploitation time window to approximately 1 min, but it is also the only way to preserve the high spin order created in the solid state at low temperatures of 1-1.5 K and moderate magnetic fields of 3.35-7 T by means of microwave irradiation. Indeed, although necessary for the DNP process to happen, the presence of free radicals in the sample would prevent its extraction as a solid for relatively longer-term storage and transport to remote locations. Moreover, for biological or clinical applications, the radical should be removed from the hyperpolarized (HP) solution. This limitation can be overcome using thermally labile ultraviolet (UV)-generated radicals that have been shown to be efficient polarizing agents, to provide a radical-free HP solution, and most importantly, to pave the way for the transport of HP solid samples to remote sites. Herein, we demonstrate that 2-keto[1-C-13]isocaproate (KIC), an important metabolic biomarker in the brain, can be highly polarized via dDNP using the nonpersistent ketyl radical generated by UV irradiation of the substrate itself. We investigated the precursor molecule and radical properties via UV-vis measurements and ESR measurements at both X-band and high field. After optimizing sample preparation and microwave irradiation conditions, we obtained 56% C-13 liquid-state polarization in 1 h by performing dDNP at 6.7 T and 1.1 +/- 0.1 K.
WOS:000587720300044
2020-10-29
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REVIEWED