Diffusion of hyperpolarized (13) C-metabolites in tumor cell spheroids using real-time NMR spectroscopy

The detection of tumors noninvasively, the characterization of their progression by defined markers and the monitoring of response to treatment are goals of medical imaging techniques. In this article, a method which measures the apparent diffusion coefficients (ADCs) of metabolites using hyperpolarized (13) C diffusion-weighted spectroscopy is presented. A pulse sequence based on the pulsed gradient spin echo (PGSE) was developed that encodes both kinetics and diffusion information. In experiments with MCF-7 human breast cancer cells, we detected an ADC of intracellularly produced lactate of 1.06 ± 0.15 µm(2) /ms, which is about one-half of the value measured with pyruvate in extracellular culture medium. When monitoring tumor cell spheroids during progressive membrane permeabilization with Triton X-100, the ratio of lactate ADC to pyruvate ADC increases as the fraction of dead cells increases. Therefore, (13) C ADC detection can yield sensitive information on changes in membrane permeability and subsequent cell death. Our results suggest that both metabolic label exchange and (13) C ADCs can be acquired simultaneously, and may potentially serve as noninvasive biomarkers for pathological changes in tumor cells.