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

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 P-31 magnetic resonance spectroscopy(MRS) employing dimethyl methylphosphonate (DMMP) as a marker of total water space, 3-aminopropylphosphonate (3-APP) asa marker of extracellular space and P-i and 3-APP as markers of intracellular pH (pH(i)) and extracellular pH (pH(e)) respectively The NIRS measurements of the tumour volumes were validated by classic radiolabelling methods using (H2O)-H-3 and [C-14]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.