The Effect of Gadolinium Doping in [¹³C₆,²H₇]Glucose Formulations on ¹³C Dynamic Nuclear Polarization at 3.35 T

Abstract

The promise of hyperpolarized glucose as a non-radioactive imaging agent capable of reporting on multiple metabolic routes has led to recent advances in its dissolution-DNP (dDNP) driven polarization using UV-light induced radicals and trityl radicals at high field (6.7 T) and 1.1 K. However, most preclinical dDNP polarizers operate at the field of 3.35 T and 1.4-1.5 K. Minute amounts of Gd 3 + complexes have shown large improvements in solid-state polarization, which can be translated to improved hyperpolarization in solution. However, this Gd 3 + effect seems to depend on magnetic field strength, metal ion concentration, and sample formulation. The effect of varying Gd 3 + concentrations at 3.35 T has been described for 13 Clabeled pyruvic acid and acetate. However, it has not been studied for other compounds at this field. The results presented here suggest that Gd 3 + doping can lead to various concentration and temperature dependent effects on the polarization of [ 13 C 6 , 2 H 7 ]glucose, not necessarily similar to the effects observed in pyruvic acid or acetate in size or direction. The maximal polarization for [ 13 C 6 , 2 H 7 ]glucose appears to be at a Gd 3 + concentration of 2 mM, when irradiating for more than 2 h at the negative maximum of the DNP intensity profile. Surprisingly, for shorter irradiation times, higher polarization levels were determined at 1.50 K compared to 1.45 K, at a [Gd 3 + ] = 1.3 mM. This was explained by the build-up time constant and maximum at these temperatures.[a] Dr.

Directly Bound Deuterons Increase X‐Nuclei Hyperpolarization using Dynamic Nuclear Polarization

“…We note that the current study on sugar formulations was carried out in formulations doped with Gd 3+ . This was done in agreement with a previous optimization study of Gd 3+ in Glc hyperpolarization [2] . The beneficial effect of Gd 3+ doping for polarization of 13 C sites agreed with prior reports on formulations that used organic:water mixtures as solvent and the same radical (OX063) [16c,20] .…”

“…Previously, the factors influencing this process in several compounds and formulations involving 13 C hyperpolarization in the solid‐state were characterized [2] . For biomedical applications, the utility of 13 C‐labeled compounds for dissolution DNP (dDNP) studies is of interest.…”

“…The dDNP approach allows enhancement of the liquid‐state polarization of 13 C sites by >10,000 fold [1a] and thus allows monitoring of metabolic processes in biological preparations and in vivo in human subjects in real time [3] . Specifically, studies have been focused on 13 C sites that are directly bound to deuterons (D), as a means to prolong the 13 C T 1 in solution, in sites that would otherwise ( i. e ., when protonated) be inaccessible to dDNP due to the fast decay of their hyperpolarized state in solution (a few seconds) [2,4] . The utility of agents of metabolic potential such as choline, D‐glucose, and 2‐deoxy‐D‐glucose, that are doubly labeled in this way, i. e .…”

“…Previously, the factors influencing this process in several compounds and formulations involving 13 C hyperpolarization in the solid-state were characterized. [2] For biomedical applications, the utility of 13 C-labeled compounds for dissolution DNP (dDNP) studies is of interest. The dDNP approach allows enhancement of the liquid-state polarization of 13 C sites by > 10,000 fold [1a] and thus allows monitoring of metabolic processes in biological preparations and in vivo in human subjects in real time.…”

Signal enhancement of hyperpolarized 15N sites in solution—increase in solid‐state polarization at 3.35 T and prolongation of relaxation in deuterated water mixtures

“…The range of Gd 3+ concentrations that was tested here resulted in similar MW irradiation profiles. The formulation with 1.3 mM Gd 3+ (a Gd 3+ concentration previously found favorable for [ 13 C 6 ,D 7 ]D‐glucose polarization as well 11 ) was tested three times to ensure reproducibility of the profile.…”