pH Dependence ofT₁for¹³C‐Labelled Small Molecules Commonly Used for Hyperpolarized Magnetic Resonance Imaging

Abstract

Hyperpolarization is a method to enhance the nuclear magnetic resonance signal by up to five orders of magnitude. However, the hyperpolarized (HP) state is transient and decays with the spin‐lattice relaxation time (T1), which is on the order of a few tens of seconds. Here, we analyzed the pH‐dependence of T1 for commonly used HP 13C‐labelled small molecules such as acetate, alanine, fumarate, lactate, pyruvate, urea and zymonic acid. For instance, the T1 of HP pyruvate is about 2.5 fold smaller at acidic pH (25 s, pH 1.7, B0=1 T) compared to pH close to physiological conditions (66 s, pH 7.3, B0=1 T). Our data shows that increasing hydronium ion concentrations shorten the T1 of protonated carboxylic acids of most of the analyzed molecules except lactate. Furthermore it suggests that intermolecular hydrogen bonding at low pH can contribute to this T1 shortening. In addition, enhanced proton exchange and chemical reactions at the pKa appear to be detrimental for the HP‐state.

Real-Time insight into in vivo redox status utilizing hyperpolarized [1-13C] N-acetyl cysteine

“…1 (C)). The polarization was much weaker at pH 2.5, suggesting a possible role for hydrogen bonds among NAC clusters in reducing the equilibrium polarization 25 , 30 . The T 1 relaxation time at 3 T of the 3.2 M [1- 13 C] NAC solution was determined to be 19.6 s by the decay dynamics of 13 C MR signal (Fig.…”

“…Samples using a standard solvent of DMSO 25 polarized poorly (Fig. 1 B), possibly because the anhydrous solvent favors the formation of intermolecular hydrogen bonds between two protonated carboxylic acid, which would increase the dipolar coupling associated with the carbonyl carbon and shorten T 1 relaxation 30 . To reduce intermolecular association, [1- 13 C] NAC was titrated to a neutral pH of 7.5 using 5 M NaOH.…”

15N-Azides as practical and effective tags for developing long-lived hyperpolarized agents

“…In comparison with other ( 15 N) 3 -azide-tagged compounds (i.e., 1-3 and 6), signal enhancements of 4 and 5 were largely affected by the acidity of the compounds. 23 Hyperpolarization of ( 15 N)3azidotyrosine 4 ( = ~142,000) and ( 15N) 3 -azidoalanine 5 ( = 80,000) was improved significantly by adding concentrated NaOH to neutralize a solution of their conjugate acids. The favorable polarization lifetime observed on ( 15 N)3-azidotyrosine 4 and ( 15 N)3-azidoalanine 5 suggested that the ( 15 N)3-azidotagging strategy offers an innovative platform, alternative to previous 15 N-labeled examples, 24 to design a diverse range of hyperpolarized amino acid imaging probes.…”

Hyperpolarization of Amino Acids in Water Utilizing Parahydrogen on a Rhodium Nanocatalyst

“…We used the acquisition scheme in Figure 1E to probe the 13 Chyperpolarizationc reatedi nt he ethyl esters 4a,b and in the free amino acids 5a,b on the same samples, with representative spectra shown in Figure 2. [12] Since the ester hydrolysis step was performed by manuali njection of the NaOD solution and because its overall length was determined by sample homogenization,w ee xpect that losses can be reduced under optimal hydrolysis conditions. We refrain from estimating the expected loss during this step, notingt he strong pH dependence of the 13 C-T 1 in a-aminoa cid.…”

“…We refrain from estimating the expected loss during this step, notingt he strong pH dependence of the 13 C-T 1 in a-aminoa cid. [12] Since the ester hydrolysis step was performed by manuali njection of the NaOD solution and because its overall length was determined by sample homogenization,w ee xpect that losses can be reduced under optimal hydrolysis conditions.…”