Estimations of intra- and extracellular volume and pH by 31P magnetic resonance spectroscopy: Effect of therapy on RIF-1 tumours

Zaver M Bhujwalla, C. L. McCoy, J. D. Glickson, R. J. Gillies, M. Stubbs

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Abstract

Quantification of metabolite or drug concentrations in living tissues requires determination of intra- and extracellular volumes. This study demonstrates how this can be achieved non-invasively by 31P magnetic resonance spectroscopy (MRS) employing dimethyl methylphosphonate (DMMP) as a marker of total water space, 3-aminopropylphosphonate (3-APP) as a marker of extracellular space and P(i) and 3-APP as markers of intracellular pH (pH(i)) and extracellular pH (pH(e)) respectively. The MRS measurements of the tumour volumes were validated by classic radiolabelling methods using 3H2O and [14C]inulin as markers of total and extracellular space respectively. The extracellular volume fraction measured by radiolabelling of RIF-1 tumours was 23 ± 0.83% (mean ± s.e.m. n = 9), not significantly different (P > 0.1) from that found by MRS (27 ± 2.9%, n = 9, London, and 35 ± 6.7, n = 14, Baltimore). In untreated RIF-1 tumours, pH(i) was about 0.2 units higher than pH(e) (P <0.01). 5-Fluorouracil (5FU) treatment (165 mg kg-1) caused no significant changes in either pH(e) or per cent extracellular volume. However significant increases in pH(i) 48 h after treatment (P <0.01) correlated with decreased tumour size and improved bioenergetic status [NTP/inorganic phosphate (P(i)) ratio]. This study shows the feasibility of an MR method (verified by a 'gold standard') for studying the effects of drug treatment on intra- and extracellular spaces and pH in solid tumours in vivo.

Original languageEnglish (US)
Pages (from-to)606-611
Number of pages6
JournalBritish Journal of Cancer
Volume78
Issue number5
Publication statusPublished - 1998

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Keywords

  • 5-Fluorouracil
  • P magnetic resonance spectroscopy
  • pH
  • Phosphonate
  • Volume fraction

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

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