Feasibility of using hyperpolarized [1-13C]lactate as a substrate for in vivo metabolic 13C MRSI studies

The development of dynamic nuclear polarization in solution has enabled in vivo C-13 MR Studies at high signal-to-noise ratio following injection of prepolarized C-13 substrates. While prior studies have demonstrated the ability to observe metabolism following injection of hyperpolarized C-13 pyruvate, the goal of this study was to develop and test a new hyperpolarized agent for investigating in vivo metabolism, [1-C-13)lactate. A preparation for prepolarized C-13 lactate and the requisite dissolution media were developed to investigate the feasibility for in vivo C-13 MRS/MRSI studies following injection of this hyperpolarized agent. This study demonstrated, for the first time, not only the ability to detect hyperpolarized [1-C-13]lactate in vivo but also the metabolic products C-13 pyruvate, C-13 alanine and C-13 bicarbonate following injection in normal rats. The use of C-13 lactate as a substrate provided the opportunity to study the conversion of lactate to pyruvate in vivo and to detect the secondary conversions to alanine and bicarbonate through pyruvate. This study also demonstrated the potential value of this hyperpolarized agent to investigate in vivo lactate uptake and metabolism in preclinical animal models. (C) 2008 Elsevier Inc. All rights reserved.