Impact of Ho³⁺-doping on ¹³C dynamic nuclear polarization using trityl OX063 free radical

Abstract

We have investigated the effects of Ho-DOTA doping on the dynamic nuclear polarization (DNP) of [1-13 C] sodium acetate using trityl OX063 free radical at 3.35 T and 1.2 K. Our results indicate that addition of 2 mM Ho-DOTA on 3 M [1-13 C] sodium acetate sample in 1:1 v/v glycerol:water with 15 mM trityl OX063 improves the DNP-enhanced 13 C solid-state nuclear polarization by a factor of around 2.7-fold. Similar to the Gd 3+ doping effect on 13 C DNP, the locations of the positive and negative 13 C maximum polarization peaks in the 13 C microwave DNP sweep are shifted towards each other with the addition of Ho-DOTA on the DNP sample. W-band electron spin resonance (ESR) studies have revealed that while the shape and linewidth of the trityl OX063 ESR spectrum was not affected by Ho 3+ -doping, the electron spin-lattice relaxation time T 1 of trityl OX063 was prominently reduced at cryogenic temperatures. The reduction of trityl OX063 electron T 1 by Ho-doping is linked to the 13 C DNP improvement in light of the thermodynamic picture of DNP. Moreover, the presence of Ho-DOTA in the dissolution liquid at room temperature has negligible reduction effect on liquid-state 13 C T 1 , in contrast to Gd 3+ -doping which drastically reduces the 13 C T 1 . The results here suggest that Ho 3+ -doping is advantageous over Gd 3+ in terms of preservation of hyperpolarized state-an important aspect to consider for in vitro and in vivo NMR or imaging (MRI) experiments where a considerable preparation time is needed to administer the hyperpolarized 13 C liquid.

Influence of Dy3+ and Tb3+ doping on 13C dynamic nuclear polarization

“…41 While a variety of Ln(iii) complexes have numerous biomedical applications, particularly in contrast-enhanced MRI, 45 only Gd 3+ and Ho 3+ have been studied extensively as beneficial doping agents in 13 C dissolution DNP. [35][36][37][38] This in part takes precedent from a previous preliminary study which has shown that only Gd 3+ and Ho 3+ ions have beneficial effects on 13 C DNP, while the other Ln(iii) ions appear to have no apparent effect on 13 C DNP enhancements for trityldoped samples. 37 We would like to note that the measurements in the aforementioned previous DNP study on using lanthanide ions 37 were not really extensively optimized in terms of concentration dependence and the fact that the optimum DNP microwave frequency could shift with lanthanide doping.…”

“…The EPR experiments were performed prior to DNP experiments, and as such optimal concentrations had not yet been determined. Previous work has shown that the optimal concentration for both gadolinium and holmium is 2 mM, 34,35,38 so this was chosen to be the concentration of terbium and dysprosium studied in order to compare their electron T 1 under the same conditions. Measurements were performed at the National High Magnetic Field Laboratory (NHMFL) in Tallahassee, FL in the W-band (94 GHz) on a Bruker E680 EPR spectrometer (Bruker Biospin, Billerica, MA) using a Bruker TE 011 cylindrical cavity.…”

“…This is in line with previous studies which have used the same method to compare DNP performance. 32,[35][36][37][38] Build-up curves were recorded and fit with single exponential equations, and using the fit, the relative polarization at 10 000 s was extrapolated.…”

“…This is in contrast to the behavior of Gd 3+ , which yields a "plateau" in polarization level improvement at concentrations between 2 and 8 mM, 37,60 but is quite similar to the "peak" behavior exhibited by Ho 3+ doping. 37,38 In Fig. 4(b), the build-up time constant is shown for each concentration of the two lanthanides.…”

“…[34][35][36][37] Recently, it was found that the addition of holmium to a trityl-doped sample results in liquid state enhancement similar to that achieved by using gadolinium. 38 While the use of these lanthanides may lead to significant polarization gains, the free ion form of these lanthanides may lead to greater toxicity of the DNP sample, which must be considered prior to in vivo biomedical application. 39 One method used to combat the toxicity of rare earth metals is to encage these lanthanide ions with a chelating agent, thus rendering them relatively inert in the body.…”