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

Br J Cancer. 1998 Sep;78(5):606-11. doi: 10.1038/bjc.1998.548.


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 and 3-APP as markers of intracellular pH (pH) and extracellular pH (pHe) 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 was about 0.2 units higher than pHe (P < 0.01). 5-Fluorouracil (5FU) treatment (165 mg kg(-1)) caused no significant changes in either pHe or per cent extracellular volume. However significant increases in pH, 48 h after treatment (P < 0.01) correlated with decreased tumour size and improved bioenergetic status [NTP/inorganic phosphate (Pi) 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.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Antimetabolites, Antineoplastic / pharmacology*
  • Extracellular Space / metabolism
  • Fluorouracil / pharmacology*
  • Hydrogen-Ion Concentration*
  • Intracellular Fluid / metabolism
  • Magnetic Resonance Spectroscopy*
  • Mice
  • Mice, Inbred C3H
  • Neoplasms, Experimental / drug therapy*
  • Neoplasms, Experimental / metabolism*
  • Organophosphorus Compounds
  • Phosphorus
  • Propylamines


  • Antimetabolites, Antineoplastic
  • Organophosphorus Compounds
  • Propylamines
  • dimethyl methylphosphonate
  • Phosphorus
  • Fluorouracil
  • 3-aminopropylphosphonic acid