A double quantum coherence transfer proton NMR spectroscopy technique for monitoring steady-state tumor lactic acid levels in vivo.

If proton nuclear magnetic resonance (1H NMR) spectroscopy is to provide a clinically useful modality for monitoring tumor growth and treatment, the technique must be able to unambiguously detect steady-state metabolite concentrations in human tumors and differentiate these from normal tissue levels. To address this problem, a two-dimensional double quantum coherence transfer spectroscopy (2DDQCT) method was developed and tested in a series of tumor cell lines implanted in mice. Lactate-edited proton NMR spectra were determined from a roughly 1-cm3 region of interest in EMT6, RIF-1, and fibroma. In two-dimensional data matrix representations of the 2DDQCT experiments (double quantum frequency on the vertical axis and chemical shift on the horizontal axis) the lactate signal (330 Hz with the transmitter set at the water resonance) was well-resolved from lipid (480 Hz, 600 Hz). The resolution in the double quantum dimension was also sufficient to conclude that a detectable level of alanine, which would reside at 358 Hz, was not present in the three tumor types. Following the NMR experiment, tumors were chemically assayed for lactate giving 8.17, 9.1, and 6.73 mumols/g wet wt for RIF-1, EMT6, and fibroma, respectively. This technique is likely to provide a noninvasive method for monitoring the steady-state lactic acid levels in small tumors before and after therapy, as well as in tissues with impaired oxygen delivery using clinical and research NMR systems.