Photogenerated Radical in Phenylglyoxylic Acid for in Vivo Hyperpolarized ¹³C MR with Photosensitive Metabolic Substrates

Whether for ¹³C magnetic resonance studies in chemistry,biochemistry, or biomedicine, hyperpolarization methods based on dynamicnuclear polarization (DNP) have become ubiquitous. DNP requires asource of unpaired electrons, which are commonly added to the sampleto be hyperpolarized in the form of stable free radicals. Once polarized,the presence of these radicals is unwanted. These radicals can bereplaced by nonpersistent radicals created by the photoirradiationof pyruvic acid (PA), which are annihilated upon dissolution or thermalizationin the solid state. However, since PA is readily metabolized by mostcells, its presence may be undesirable for some metabolic studies.In addition, some ¹³C substrates are photosensitive andtherefore may degrade during the photogeneration of a PA radical,which requires ultraviolet (UV) light. We show here that the photoirradiationof phenylglyoxylic acid (PhGA) using visible light produces a nonpersistentradical that, in principle, can be used to hyperpolarize any molecule.We compare radical yields in samples containing PA and PhGA upon photoirradiationwith broadband and narrowband UV–visible light sources. Todemonstrate the suitability of PhGA as a radical precursor for DNP,we polarized the gluconeogenic probe ¹³C-dihydroxyacetone,which is UV-sensitive, using a commercial 3.35 T DNP polarizer andthen injected this into a mouse and followed its metabolism in vivo.