Hyperpolarized Y-89 complexes are attractive NMR spectroscopy and MR imaging probes due to the exceptionally long spin-lattice relaxation time (T-1 approximate to 10 min) of the (89)y nucleus. However, in vivo imaging of Y-89 has not yet been realized because of the low NMR signal enhancement levels previously achieved for this ultra low-gamma(n) nucleus. Here, we report liquid-state Y-89 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 Y-89 DNP was shown to proceed by thermal mixing and the liquid state Y-89. 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-C-13]pyruvate showed that both Y-89 and C-13 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-gamma(n) nuclei.