Abstract
Parahydrogen-induced polarization of 13C nuclei by side-arm hydrogenation (PHIP-SAH) for [1-13C]acetate and [1-13C]pyruvate esters with application of PH-INEPT-type pulse sequences for 1H to 13C polarization transfer is reported, and its efficiency is compared with that of polarization transfer based on magnetic field cycling (MFC). The pulse-sequence transfer approach may have its merits in some applications because the entire hyperpolarization procedure is implemented directly in an NMR or MRI instrument, whereas MFC requires a controlled field variation at low magnetic fields. Optimization of the PH-INEPT-type transfer sequences resulted in 13C polarization values of 0.66 ± 0.04% and 0.19 ± 0.02% for allyl [1-13C]pyruvate and ethyl [1-13C]acetate, respectively, which is lower than the corresponding polarization levels obtained with MFC for 1H to 13C polarization transfer (3.95 ± 0.05% and 0.65 ± 0.05% for allyl [1-13C]pyruvate and ethyl [1-13C]acetate, respectively). Nevertheless, a significant 13C NMR signal enhancement with respect to thermal polarization allowed us to perform 13C MR imaging of both biologically relevant hyperpolarized molecules which can be used to produce useful contrast agents for the in vivo imaging applications.
Highlights
Parahydrogen-induced polarization of 13C nuclei by side-arm hydrogenation (PHIP-SAH) for [1-13C] acetate and [1-13C]pyruvate esters with application of PH-INEPT-type pulse sequences for 1H to 13C polarization transfer is reported, and its efficiency is compared with that of polarization transfer based on magnetic field cycling (MFC)
Complementary to 13C-labeled glucose widely employed in metabolic studies[1], acetate is used in the magnetic resonance (MR) studies of metabolism in b rain2–4, liver[5], and muscles[6,7], in particular, to address the tricarboxylic acid cycle, which is the main cycle in energy homeostasis in animals[2,8,9] and humans[10]
To estimate an optimal magnetic field for polarization transfer, MFC experiments were performed by changing the field inside the magnetic shield mounted on top of a spectrometer using an automated MFC setup described elsewhere[44]
Summary
Parahydrogen-induced polarization of 13C nuclei by side-arm hydrogenation (PHIP-SAH) for [1-13C] acetate and [1-13C]pyruvate esters with application of PH-INEPT-type pulse sequences for 1H to 13C polarization transfer is reported, and its efficiency is compared with that of polarization transfer based on magnetic field cycling (MFC). Under in vivo conditions the T 1 relaxation time of lactate methyl protons is only 1.7 s, while the carboxyl carbon T 1 time is 30 s for [1-13C]pyruvate[21] This provides a sufficient time window for the preparation, administration and circulation of 13C-hyperpolarized metabolites and for monitoring their metabolic pathways. Dissolution dynamic nuclear polarization (d-DNP)[22] is the leading hyperpolarization technique for in vivo applications, with the majority of all MRI studies utilizing hyperpolarized (HP) 13C-labeled pyruvate and acetate as well as other metabolites being performed using d-DNP23. Reineri et al produced HP acetate by hydrogenation of vinyl acetate to ethyl acetate, followed by 1H to 13C polarization transfer via magnetic field cycling and subsequent hydrolysis of ethyl acetate with sodium h ydroxide[28] Subsequent studies extended this approach to lactate[29] and pyruvate[30,31]. PHIP-SAH technique rekindled the interest in p-H2based approaches for the production of HP contrast agents for in vivo MR metabolic studies
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