31 P nmr spectroscopy studies of phopholipid metabolism in human melanoma xenograft lines differing in rate of tumour cell proliferation

The concentration of phospholipid metabolites in tumours has been hypothesized to be related to rate of cell membrane turnover and may reflect rate of cell proliferation. The purpose of the study reported here was to investigate whether 31 P NMR resonance ratios involving the phosphomonoester (PME) or phosphodiester (PDE) resonance are correlated to fraction of cells in S‐phase or volume‐doubling time in experimental tumours. Four human melanoma xenograft lines (BEX‐t, HUX‐t, SAX‐t, WIX‐t) were included in the study. The tumours were grown subcutaneously in male BALB/c‐nu/nu mice. 31 P NMR spectroscopy was performed at a magnetic field strength of 4.7 T. Fraction of cells in S‐phase was measured by flow cytometry. Tumour volume‐doubling time was determined by Gompertzian analysis of volumetric growth data. BEX‐t and SAX‐t tumours differed in fraction of cells in S‐phase and volume‐doubling time, but showed similar 31 P NMR resonance ratios. BEX‐t and WIX‐t tumours showed significantly different 31 P NMR resonance ratios but similar fractions of cells in S‐phase. The 31 P NMR resonance ratios were significantly different for small and large HUX‐t tumours even though fraction of cells in S‐phase and volume‐doubling time did not differ with tumour volume. None of the 31 P NMR resonance ratios showed significant increase with increasing fraction of cells in S‐phase or significant decrease with increasing tumour volume‐doubling time across the four xenograft lines. Consequently, the PME and PDE resonances of 31 P NMR spectra recorded in vivo are probably of limited value in assessment of rate of cell proliferation in tumours and hence also in prediction of tumour treatment resistance caused by rapid cell proliferation.