Impact of Gd ³⁺ on DNP of [1- ¹³C]pyruvate doped with trityl OX063, BDPA, or 4-oxo-TEMPO

Hyperpolarized [1- ¹³C]pyruvate has become an important diagnostic tracer of normal and aberrant cellular metabolism for in vitro and in vivo NMR spectroscopy (MRS) and imaging (MRI). In pursuit of achieving high NMR signal enhancements in dynamic nuclear polarization (DNP) experiments, we have performed an extensive investigation of the influence of Gd ³⁺ doping, a parameter previously reported to improve hyperpolarized NMR signals, on the DNP of this compound. [1- ¹³C]Pyruvate samples were doped with varying amounts of Gd ³⁺ and fixed optimal concentrations of free radical polarizing agents commonly used in fast dissolution DNP: trityl OX063 (15 mM), 4-oxo-TEMPO (40 mM), and BDPA (40 mM). In general, we have observed three regions of interest, namely, (i) a monotonic increase in DNP-enhanced nuclear polarization P _dnp upon increasing the Gd ³⁺ concentration until a certain threshold concentration c ₁ (1-2 mM) is reached, (ii) a region of roughly constant maximum P _dnp from c ₁ until a concentration threshold c ₂ (4-5 mM), and (iii) a monotonic decrease in P _dnp at Gd ³⁺ concentration c > c ₂. Of the three free radical polarizing agents used, trityl OX063 gave the best response to Gd ³⁺ doping, with a 300% increase in the solid-state nuclear polarization, whereas addition of the optimum Gd ³⁺ concentration on BDPA and 4-oxo-TEMPO-doped samples only yielded a relatively modest 5-20% increase in the base DNP-enhanced polarization. The increase in P _dnp due to Gd ³⁺ doping is ascribed to the decrease in the electronic spin-lattice relaxation T _1e of the free radical electrons, which plays a role in achieving lower spin temperature T _s of the nuclear Zeeman system. These results are discussed qualitatively in terms of the spin temperature model of DNP.