A Field‐Independent Method for the Rapid Generation of Hyperpolarized [1‐¹³C]Pyruvate in Clean Water Solutions for Biomedical Applications

Abstract

Hyperpolarization methods in magnetic resonance enhance the signals by several orders of magnitude, opening new windows for real‐time investigations of dynamic processes in vitro and in vivo. Here, we propose a field‐independent para‐hydrogen‐based pulsed method to produce rapidly hyperpolarized 13C‐labeled substrates. We demonstrate the method by polarizing the carboxylic carbon of the pyruvate moiety in a purposely designed precursor to 24 % at ≈22 mT. Following a fast purification procedure, we measure 8 % polarization on free [1‐13C]pyruvate in clean water solutions at physiological conditions at 7 T. The enhanced signals allow real‐time monitoring of the pyruvate‐lactate conversion in cancer cells, demonstrating the potential of the method for biomedical applications in combination with existing or developing magnetic resonance technologies.

Parahydrogen-induced polarization and spin order transfer in ethyl pyruvate at high magnetic fields

“…Although for in vivo murine experiments no more than 200–500 μL are needed for the injection, the residual sample is often used for quality control (pH measurements, polarization quantification, and concentration quantification). 60 and 24% 13 C polarization for 13 and 55 mM concentrations of 0.1 mL pyruvate precursors solution were reported recently by Glöggler and coworkers 21 , 68 , which corresponds to 0.78 and 1.32 M% molar polarization and 0.078 and 0.132 mmol% molecular polarization, respectively. In our work, we achieved 17.4% 13 C polarization for 100 mM concentration of 1 mL 1- 13 C-EP- d6 solution, corresponding to 1.74 M% molar polarization and 1.74 mmol%.…”

Catalyst-Free Aqueous Hyperpolarized [1-13C]Pyruvate Obtained by Re-Dissolution Signal Amplification by Reversible Exchange

“…Two fast hyperpolarization approaches have been introduced for [1- 13 C]­pyruvate using the spin order provided by parahydrogen (p-H 2 )the nuclear spin singlet state isomer of H 2 gas. − Reineri et al have employed the Parahydrogen Induced Polarization (PHIP) method , to hydrogenate an unsaturated side arm of esterified [1- 13 C]­pyruvate; this side arm hydrogenation (SAH) PHIP method has now been utilized and adapted by several groups. − Cleavage of the side arm and extraction into aqueous media was demonstrated in a few studies. − Duckett et al pioneered the non-hydrogenative Signal Amplification by Reversible Exchange (SABRE) approach . This method is based on the simultaneous, temporary binding of a substrate and p -H 2 to an Ir-hexacoordinate complex.…”

Combined Homogeneous and Heterogeneous Hydrogenation with Parahydrogen to Yield Catalyst-Free Solutions of Hyperpolarized [1-13C]Succinate

“…1,2 Parahydrogen-induced polarization (PHIP) has emerged as an inexpensive contrast-agent hyperpolarization method. [3][4][5][6][7][8][9][10][11] Parahydrogen (p-H2) can be readily prepared by cooling hydrogen gas to ≲30 K, and then catalytically reacted with an unsaturated precursor to produce a hyperpolarized product molecule. 12,13 The hyperpolarization is transferred to a 13 C spin in the molecule, [14][15][16][17][18][19][20] and then the hyperpolarized molecule can be injected for in vivo imaging, 15,21,22 and more recent work has allowed for purification prior to injection.…”