A platform for designing hyperpolarized magnetic resonance chemical probes

Abstract

Hyperpolarization is a highly promising technique for improving the sensitivity of magnetic resonance chemical probes. Here we report [15N, D9]trimethylphenylammonium as a platform for designing a variety of hyperpolarized magnetic resonance chemical probes. The platform structure shows a remarkably long 15N spin–lattice relaxation value (816 s, 14.1 T) for retaining its hyperpolarized spin state. The extended lifetime enables the detection of the hyperpolarized 15N signal of the platform for several tens of minutes and thus overcomes the intrinsic short analysis time of hyperpolarized probes. Versatility of the platform is demonstrated by applying it to three types of hyperpolarized chemical probes: one each for sensing calcium ions, reactive oxygen species (hydrogen peroxide) and enzyme activity (carboxyl esterase). All of the designed probes achieve high sensitivity with rapid reactions and chemical shift changes, which are sufficient to allow sensitive and real-time monitoring of target molecules by 15N magnetic resonance.

Design of a 15N Molecular Unit to Achieve Long Retention of Hyperpolarized Spin State

“…The 15 N atom in [ 15 N, D 9 ]TMPA 2 has no 1 H within two bonds, which could explain the long T 1 achieved18. However, unexpectedly, it was found that TMPA 2 was still affected by 15 N– 1 H DD relaxation.…”

“…To address this crucial issue, attention has focused on the development of molecular units that can retain the hyperpolarized state for longer periods101112131415161718. The hyperpolarization lifetime is directly correlated with the spin–lattice relaxation time ( T 1 ) of nuclei.…”

“…1). The quaternary 15 N atoms of 1 and 2 have a long T 1 of 275 and 816 s (14.1 T, 30 °C, D 2 O), respectively18. By utilizing the unit as a platform, three types of hyperpolarized molecular sensors were designed.…”

Observation of Glycolytic Metabolites in Tumor Cell Lysate by Using Hyperpolarization of Deuterated Glucose

“…During our investigation of useful DNP substrates, 32,33) we have measured 13 C-NMR spectra of several deuterated glucoses hyperpolarized by DNP, and have found that the hyperpolarized C-perdeuterated glucose exhibited a larger enhancement and slower decay of signal than those with a Cprotonated glucose. 34) This manuscript details the 13 C-NMR profiles of hyperpolarized 13 C 6 -Glc-d 7 (1) and compares with those of 13 C 6 -glucose (2, 13 C 6 -Glc).…”

Hyperpolarised organic phosphates as NMR reporters of compartmental pH

“…High-field NMR affords sufficiently accurate chemical shift measurements to identify cytosolic pH concurrently to 4 The use of alternative substrates with longer T 1 times could facilitate the detection of intracellular organic phosphates with hyperpolarized NMR. As an example, hyperpolarized [2][3][4][5][6][7][8][9][10][11][12][13] C]-glycerone has recently allowed the detection of at least five different organic phosphate metabolites in a perfused liver model. 11 These studies encourage the hope that rapid and noninvasive imaging of compartmental pH may become feasible through hyperpolarised …”