Lymphocyte metabolism and cytotoxic activity monitored with 31P magnetic resonance spectroscopy

Continuous metabolic monitoring of human lymphocytes and a tumor cell line was achieved by means of nuclear magnetic resonance (NMR) applied to cells suspended in alginate gels. Human peripheral blood lymphocytes cultured in vitro were examined with 31P magnetic resonance spectroscopy (MRS) before and after activation with phytohemagglutinin and interleukin-2 (IL-2). Following the addition of these biological response modifiers, increases in [ATP], phosphomonoesters (PME), and phosphodiesters occurred. These appear to be markers of lymphocyte stimulation. Lymphocyte pH was unchanged. A target tumor cell line (K562) showed 31P NMR spectra that differed significantly from that of lymphocytes. When lymphocytes were mixed with tumor cells (to induce tumor cell death), and monitored by 31P MRS, levels of inorganic phosphate (Pi) increased, [PME] levels fell, and release of H+ was inhibited. 31P MRS may therefore provide a noninvasive assay of lymphocyte-mediated tumor cell killing that will have application in monitoring treatment in patients undergoing this type of therapy.