Hybrid polarizing solids for pure hyperpolarized liquids through dissolution dynamic nuclear polarization

David Gajan; Aurélien Bornet; Basile Vuichoud; Jonas Milani; Roberto Melzi; Henri A. van Kalkeren; Laurent Veyre; Chloé Thieuleux; Matthew P. Conley; Wolfram R. Grüning; Martin Schwarzwälder; Anne Lesage; Christophe Copéret; Geoffrey Bodenhausen; Lyndon Emsley; Sami Jannin

doi:10.1073/pnas.1407730111

New Research In

Edited* by Timothy M. Swager, Massachusetts Institute of Technology, Cambridge, MA, and approved August 25, 2014 (received for review April 30, 2014)

Significance

Hyperpolarization by dissolution dynamic nuclear polarization can dramatically enhance signal intensities in MRI and NMR, notably for metabolic tracers for imaging and diagnosis. It is applicable to a variety of substrates for in vivo imaging and chemistry but requires the use of contaminants (glassing agents and free radicals) that may interact with cells and proteins and can have potential side effects. These contaminants can sometimes be eliminated by precipitation followed by filtration or solvent extraction, but these methods are substrate-specific, are usually time-consuming, and typically result in signal loss. Here, production of pure hyperpolarized liquids free of contaminants is shown by a simple wetting–polarization–filtration sequence for a solid silica matrix containing homogeneously distributed persistent radicals.

Abstract

Hyperpolarization of substrates for magnetic resonance spectroscopy (MRS) and imaging (MRI) by dissolution dynamic nuclear polarization (D-DNP) 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 can raise concerns for in vivo MRI applications, such as perturbing molecular interactions, and may induce the erosion of hyperpolarization in spectroscopy and MRI. We show that D-DNP can be performed efficiently with hybrid polarizing solids (HYPSOs) with 2,2,6,6-tetramethyl-piperidine-1-oxyl radicals incorporated in a mesostructured silica material and homogeneously distributed along its pore channels. The powder is wetted with a solution containing molecules of interest (for example, metabolites for MRS or MRI) to fill the pore channels (incipient wetness impregnation), and DNP is performed at low temperatures in a very efficient manner. This approach allows high polarization without the need for glass-forming agents and is applicable to a broad range of substrates, including peptides and metabolites. During dissolution, HYPSO is physically retained by simple filtration in the cryostat of 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 other pollutants, and is ready for in vivo infusion.

Footnotes

↵¹To whom correspondence should be addressed. Email: lyndon.emsley{at}ens-lyon.fr.

Author contributions: D.G., A.L., C.C., G.B., L.E., and S.J. designed research; D.G., A.B., B.V., J.M., H.A.v.K., L.V., M.P.C., W.R.G., M.S., and S.J. performed research; H.A.v.K., M.P.C., W.R.G., and M.S. contributed new reagents/analytic tools; D.G., A.B., B.V., J.M., R.M., C.T., A.L., C.C., G.B., L.E., and S.J. analyzed data; and D.G., C.T., C.C., G.B., L.E., and S.J. wrote the paper.
The authors declare no conflict of interest.
↵*This Direct Submission article had a prearranged editor.
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