Chemical Exchange Reaction Effect on Polarization Transfer Efficiency in SLIC-SABRE

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Signal Amplificationb yR eversible Exchange (SABRE)i sapromising methodf or NMR signal enhancement and production of hyperpolarizedm olecules. As nuclear spin relaxation times of heteronuclei are usually much longer than those of protons, SABRE-based hyperpolarization of heteronuclei in molecules is highly important in the context of biomedical applications.I nt his work, we demonstrate that the SLIC-SABRE technique can be successfully used to hyperpolarize 15 Nn uclei in dalfampridine.T he high polarization level of ca. 8% achieved in this work made it possible to acquire 15 NM Rimages at naturala bundance of the 15 Nn uclei for the first time.Dalfampridine (FAM), or 4-aminopyridine, is ad rug that can significantlyr educet he symptoms of multiple sclerosis. [1] FAM does not affect the course of the disease itself, but it is employed for symptomatic improvement of walking in adults with several variations of the disease. [2,3] Its action is based on blockingo fp otassium channels.I tl eads to the increaseo ft he action potentialc onduction in the demyelinated nerve fibers. [2,3] This drug is approved by the regulating agencies in the US, Canada, and Europe, andi ti sm arketed as Ampyraa nd Fampyra.T he distribution of the drug inside the body,t he biochemicalpathways of its transformation,aswellasits metabolic profile are important information for determining the effectivenesso ft he drug. Magnetic resonancei maging (MRI),b eing an on-invasive method with ah igh information content,a llows one to effectively obtain these unique data.H owever,n uclear magnetic resonance (NMR) and MRI have ar elatively low sensitivity. [4] This is due to the fact that populationdifferenceo fn uclear spin states (termed nuclear spin polarization P)i ss mall. For 1 Hn uclei, thermal polarization is only 1.02 10 À5 in a3T magnetic field, [4] and for other NMR-active spin-1/2 nuclei (e.g., 13 C, 15 N, 19 F, 31 P) with their lower gyromagnetic ratiosi ti se ven less. While this polarization level is sufficient for performing in vivo MRI based on the 1 HNMR signald etection of tissue water, performing in vivo 1 HM RI for any other molecules against the strongb ackground of water signal is highlyu nfavorable.T he use of heteronuclei (e.g., 15 N) mitigatest his problem,b ecause their concentration in tissuesi ss ignificantly lower in comparison with 1 H. More importantly,t hese nucleio ften have very long T 1 relaxation times up to ten minutes, [5] which is very usefulwhen transientnon-equilibrium spin polarizationsare involved( see below).Aw ide range of biologically relevant molecules, such as nitrogenousb ases, DNA, RNA, amino acids, peptides, proteins, vitamins, hormones, and drugs contain nitrogen atoms. The directu se of at hermally polarized signal of 15 Nn uclei for in vivo MRI applicationsi sv ery challenging because of the very low natural abundance of the 15 Ni sotope (0.365 %) and the lowerg yromagnetic ratio of 15 Nn uclei compared to 1 H ( % 1:10), resulting in low detection sensitivity.Asaresult, alimited number of 15 NM RI...

mentioning

confidence: 99%

¹⁵N Hyperpolarization of Dalfampridine at Natural Abundance for Magnetic Resonance Imaging

Skovpin

Svyatova

Чуканов

et al. 2019

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“…[43,44] The temperature dependence of the polarization was well reproduced. [43,44] The temperature dependence of the polarization was well reproduced.…”

Section: Theorymentioning

confidence: 75%

“…This library has already been used to simulate SLIC-SABRE [44] with the "quantitative SABRE model". [54] Thec ode with ad escriptiona nd various examples is available online.…”

Section: Moin Librarymentioning

confidence: 99%

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Front Cover: Simulating Non‐linear Chemical and Physical (CAP) Dynamics of Signal Amplification By Reversible Exchange (SABRE) (Chem. Eur. J. 32/2019)

Pravdivtsev

Hövener

2019

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The hyperpolarization of nuclear spins by using parahydrogen (pH 2 )i saf ascinating technique that allows spin polarization and thus the magnetic resonance signal to be increased by severalo rders of magnitude. Entirely new applicationshave become available. Signal amplification by reversible exchange (SABRE)i sarelatively new method that is based on the reversible exchange of as ubstrate, catalyst and parahydrogen. SABRE is particularly interesting for in vivo medical andi ndustrial applications,s uch as fast and low-cost trace analysiso rc ontinuouss ignal enhancement. Ever since its discovery, many attempts have been made to model andu nderstand SABRE, with various degreeso fs implifications. In this work, we reduced the simplifications further,t aking into account non-linearc hemical and physical (CAP)d ynamics of several multi-spin systems. Am aster equationw as derivedandr ealized using the MOIN opensources oftware. The effectso fd ifferent parameters (exchange rates,c oncentrations,s pin-spin couplings) on relaxation and the polarization level have been evaluated and the resultsp rovide interesting insights into the mechanism of SABRE.[a] Dr.A .N.Pravdivtsev,P rof. Dr.J.-B. Hçvener Section Biomedical Imaging Molecular Imaging North CompetenceC enter (MOINCC)Supporting information and the ORCID identification number(s) for the author(s) of this article can be found under: https://doi.org/10.1002/chem.201806133.T he Supporting information contains an evaluation of the CAP model master equation and NMR parameters of the S, IrH 2 S a S e , IrH 2 S a S e 2 and H 2 systems.

“…Specifically, we hyperpolarized 15 N‐pyridine ( 15 N‐Py) and 1‐ 15 N‐nicotinamide ( 15 N‐NA) via SLIC‐SABRE at the high field of an MRI scanner. The parameters for the SLIC‐SABRE of 15 N‐Py were similar to those optimized and reported before: amplitude of RF‐pulse, ν 1 =5 Hz, offset from the center of bound 15 N‐Py resonance, Δ rf

≅

17 Hz and duration of continuous wave (CW) RF‐pulse, t cw =1.17 s . For 15 N‐NA, we used the same parameters of SLIC‐SABRE ( ν 1 , Δ rf , t cw ) because when attached to the active SABRE complex it has similar J ‐coupling constants with hydride protons coming from pH 2 .…”

Section: Experimental Designmentioning

confidence: 99%

¹⁵N MRI of SLIC‐SABRE Hyperpolarized ¹⁵N‐Labelled Pyridine and Nicotinamide

Svyatova

Skovpin

Чуканов

et al. 2019

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Magnetic Resonance Imaging (MRI) is a powerful non‐invasive diagnostic method extensively used in biomedical studies. A significant limitation of MRI is its relatively low signal‐to‐noise ratio, which can be increased by hyperpolarizing nuclear spins. One promising method is Signal Amplification By Reversible Exchange (SABRE), which employs parahydrogen as a source of hyperpolarization. Recent studies demonstrated the feasibility to improve MRI sensitivity with this hyperpolarization technique. Hyperpolarized 15N nuclei in biomolecules can potentially retain their spin alignment for tens of minutes, providing an extended time window for the utilization of the hyperpolarized compounds. In this work, we demonstrate for the first time that radio‐frequency‐based SABRE hyperpolarization techniques can be used to obtain 15N MRI of biomolecule 1‐15N‐nicotinamide. Two image acquisition strategies were utilized and compared: Single Point Imaging (SPI) and Fast Low Angle SHot (FLASH). These methods demonstrated opportunities of high‐field SABRE for biomedical applications.