We wish to understand differences in metabolism and regulation between normal and cancer cells, and between cancer that are responsive to chemotherapy and those that exhibit multiple drug resistance (MDR). Nuclear magnetic resonance (NMR) spectroscopy is used to monitor metabolic processes noninvasively, using a perfusion technique that we have developed in which cells are embedded in gel threads. With this technique, we have observed with 31P NMR significant differences in the levels of major phosphate metabolites in wild type (WT) MCF-7 breast cancer cells, and an adriamycin cell line (AdrR) that exhibits MDR. One of the major differences between normal and cancer cells, is the control of energy metabolism. To follow glycolysis in WT and AdrR cells we use improved the perfusion technique to enable us to use small volumes with 13C-glucose and areable to monitor the rate of glucose uptake and the concomitant rate of lactate production with 13C NMR. The effects of inhibitors on glycolisis have been monitored in the perfusion system. Phospholipid metabolism in these cells has also been monitored by consideration of the levels of phosphomonester (PME) and phosphodiester (PDE) peaks in the 31P NMR spectra. In general, we have found that the higher the PME peak, the more rapidly proliferating are the cells. These results together may provide spectroscopic markers for clinical distinction of growths. In order to extend these observations to noninvasive metabolic measurements in vivo, we have designed and constructed a versatile NMR probe for our spectrometer. All components are adjustable and replaceable, but currently we observe spectra from a subcutaneous tumor in a rodent. We anticipate extending these studies to larger animals and to clinical trials of 31P MRS of breast nodes and limb growths.
