DNP by Thermal Mixing under Optimized Conditions Yields > 60 000-fold Enhancement of Y-89 NMR Signal

Advanced Imaging Research Center, University of Texas Southwestern Medical Center, 5323 Harry Hines Boulevard, Dallas, Texas 75390, USA.
Journal of the American Chemical Society (Impact Factor: 12.11). 06/2011; 133(22):8673-80. DOI: 10.1021/ja201880y
Source: PubMed


Hyperpolarized (89)Y complexes are attractive NMR spectroscopy and MR imaging probes due to the exceptionally long spin-lattice relaxation time (T(1) ≈ 10 min) of the (89)Y nucleus. However, in vivo imaging of (89)Y has not yet been realized because of the low NMR signal enhancement levels previously achieved for this ultra low-γ(n) nucleus. Here, we report liquid-state (89)Y NMR signal enhancements over 60,000 times the thermal signal at 298 K in a 9.4 T magnet, achieved after the dynamic nuclear polarization (DNP) of Y(III) complex of 1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid (DOTA) samples at 3.35 T and 1.4 K. The (89)Y DNP was shown to proceed by thermal mixing and the liquid state (89)Y NMR signal enhancement was maximized by (i) establishing the optimal microwave irradiation frequency, (ii) optimizing the glassing matrix, (iii) choosing a radical with negligible inhomogeneous line broadening contribution to the ESR linewidth, and (iv) addition of an electron T(1e) relaxation agent. The highest enhancements were achieved using a trityl OX063 radical combined with a gadolinium relaxation agent in water-glycerol matrix. Co-polarization of (89)YDOTA and sodium [1-(13)C]pyruvate showed that both (89)Y and (13)C nuclear species acquired the same spin temperature, consistent with thermal mixing theory of DNP. This methodology may be applicable for the optimization of DNP of other low-γ(n) nuclei.

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Available from: Lloyd Lumata, Oct 09, 2015
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    • "The sequence used for the acquisition consisted of a series of small flip angle pulses (5° for [ 13 C]/[ 13 C, 15 N]urea and 10° for [5- 13 C]/ [ 13 C, 15 N]glutamine). The liquid polarization values and 13 C T 1 times were corrected for induced decay from the RF read-out pulses (flip angle correction [15]; Eqs. (3) and (4), respectively). "
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    ABSTRACT: The yttrium complex of 1,4,7,10-tetraazacyclododecane-1,4,7,10-tetra(1′-13C-acetic acid) [13C]DOTA was synthesized. Fast dissolution dynamic nuclear polarization (DNP) nuclear magnetic resonance (NMR) studies revealed that the 89Y, 13C, and 15N nuclei present in the complex could be co-polarized at the same optimum microwave irradiation frequency. The liquid-state spin–lattice relaxation time T 1 of these nuclei were found to be reasonably long to preserve some or most of the DNP-enhanced polarization after dissolution. The hyperpolarized 13C and 89Y NMR signals were optimized in different glassing mixtures. The overall results are discussed in light of the thermal mixing model of DNP.
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