UV-Irradiated 2-Keto-(1-¹³C)IsocaproicAcid for High-Performance ¹³C Hyperpolarized MR

Enhancing the sensitivity of magneticresonance spectroscopy/imaging(MRS/MRI) by dissolution dynamic nuclear polarization (dDNP) has expandedthe scope of MRS applications to new fields of research. Most importantly,it has paved the way toward noninvasive studies of the fate of a metabolitein real time. As its name implies, in a typical dDNP experiment, thehyperpolarized (HP) sample is extracted from the polarizer in theliquid state. This procedure limits the HP signal exploitation timewindow to approximately 1 min, but it is also the only way to preservethe high spin order created in the solid state at low temperaturesof 1–1.5 K and moderate magnetic fields of 3.35–7 Tby means of microwave irradiation. Indeed, although necessary forthe DNP process to happen, the presence of free radicals in the samplewould prevent its extraction as a solid for relatively longer-termstorage and transport to remote locations. Moreover, for biologicalor clinical applications, the radical should be removed from the hyperpolarized(HP) solution. This limitation can be overcome using thermally labileultraviolet (UV)-generated radicals that have been shown to be efficientpolarizing agents, to provide a radical-free HP solution, and mostimportantly, to pave the way for the transport of HP solid samplesto remote sites. Herein, we demonstrate that 2-keto[1-¹³C]isocaproate (KIC), an important metabolic biomarker in the brain,can be highly polarized via dDNP using the nonpersistentketyl 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 bothX-band and high field. After optimizing sample preparation and microwaveirradiation conditions, we obtained 56% ¹³C liquid-statepolarization in 1 h by performing dDNP at 6.7 T and 1.1 ± 0.1K.