Hybrid Polarizing Solids for Pure Hyperpolarized

Hybrid Polarizing Solids for Pure Hyperpolarized Analytes
through Dissolution Dynamic Nuclear Polarization
David Gajana, Aurélien Bornetb, Basile Vuichoudb, Jonas Milanib, Roberto Melzic, Laurent Veyred, Chloé Thieuleuxd, Matthew P.
Conley e, Wolfram R. Grüning e, Martin Schwarzwäldere, Anne Lesage,a Christophe Copérete, Geoffrey Bodenhausenb,f,g,h, Lyndon
Emsley,a and Sami Janninb,i
a Centre de RMN à Très Hauts Champs, Institut de Sciences Analytiques (CNRS / ENS Lyon / UCB Lyon 1), Université de Lyon,
69100 Villeurbanne, France.
b Institut des Sciences et Ingénierie Chimiques, Ecole Polytechnique Fédérale de Lausanne (EPFL), Batochime, CH-1015 Lausanne,
Switzerland.
c Bruker Italia S.r.l. Viale V. Lancetti 43, 20158 Milano, Italy.
d Université de Lyon, Institut de Chimie de Lyon, LC2P2, UMR 5265 CNRS-CPE Lyon-UCBL, CPE Lyon, 43 Bvd du 11 Novembre
1918, 69100 Villeurbanne, France.
e ETH Zürich, Department of Chemistry and Applied Biosciences, Wolfgang-Pauli-Strasse 10 8093 Zürich, Switzerland.
f Département de Chimie, Ecole Normale Supérieure, 24 Rue Lhomond, 75231 Paris Cedex 05, France.
g Université Pierre-et-Marie Curie, Paris, France.
h UMR 7203, CNRS/UPMC/ENS, Paris, France.
i Bruker BioSpin AG, Industriestrasse 26, 8117 Fällanden, Switzerland.
Hyperpolarization of substrates for magnetic resonance spectroscopy (MRS)
and imaging (MRI) by Dissolution Dynamic Nuclear Polarization (D-DNP)
[1] usually involves saturating the ESR transitions of polarizing agents (PAs),
e.g. persistent radicals embedded in frozen glassy matrices. This approach has
shown enormous potential to achieve greatly enhanced nuclear spin
polarization, but the presence of PAs and/or glassing agents in the sample
after dissolution poses serious toxicology issues for in-vivo MRI applications,
may perturb molecular interactions and leads to the erosion of
hyperpolarization in both spectroscopy and MRI. We demonstrate that DDNP with Cross Polarization (CP) [2] can be performed efficiently with a
new generation of hybrid polarizing solids (HYPSO) with TEMPO radicals
incorporated in a mesostructured silica material and homogeneously
distributed along the pore channels (see figure 1) [3]. The powder is wetted
with a solution containing molecules of interest for MRS or MRI (for
example metabolites) to fill the pore channels (Incipient Wetness
Impregnation), and DNP is performed at low temperatures in a very efficient
manner. This approach does not require addition of glass-forming agents.
During dissolution, HYPSO is physically retained by simple filtration in the
DNP polarizer and a pure hyperpolarized solution is collected within a few
seconds. The resulting solution contains the pure substrate, is free from any
paramagnetic or toxic pollutants and ready for in-vivo infusion. HYPSO
enables delicate experiments such as drug screening with pure hyperpolarized
solutions. Our latest results in this field will be presented. We advocate the
use of HYPSO for its universal applicability and its low toxicity.
[1] Ardenkjaer-Larsen JH, Fridlund B, Gram A, Hansson G, Hansson L,
Lerche MH, Servin R, Thaning M, & Golman K (2003) Increase in signal-toFigure 1. (a) HYPSO-1.0 is impregnated with a [113
C]pyruvate solution without addition of any glass-forming
noise ratio of > 10,000 times in liquid-state NMR. Proc. Natl. Acad. Sci. USA
agents. (b) DNP is achieved by microwave irradiation of the
100(18):10158-10163.
PA and optionally Cross Polarization. (c) The polarized
[2] Bornet A., Melzi R., Perez Linde A. J., Hautle P., van den Brandt B.,
solution is expulsed from HYPSO-1.0 by injecting
Jannin S, Bodenhausen G. (2013) Boosting Dissolution Dynamic Nuclear
superheated water. The polarization of the pure
hyperpolarized solution amounts to P(13C) = 25.3 %.
Polarization by Cross Polarization. J. Phys. Chem. Lett., 4:111–114.
[3] Gajan D, Schwarzwälder M, Conley MP, Grüning W, Rossini AJ,
Zagdoun A, Lelli M, Yulikov M, Jeschke G, Ouari O, Tordo P, Veyre L,
Thieuleux C, Lesage A, Emsley L, & Copéret C (2013) Solid-phase polarizing matrices for dynamic nuclear polarization from
homogeneously distributed radicals in mesostructured hybrid silica materials. J. Am. Chem. Soc. 135:15459.

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