Zm. Bhujwalla et al., ESTIMATIONS OF INTRACELLULAR AND EXTRACELLULAR VOLUME AND PH BY P-31 MAGNETIC-RESONANCE SPECTROSCOPY - EFFECT OF THERAPY ON RIF-1 TUMORS, British Journal of Cancer, 78(5), 1998, pp. 606-611
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 (DMM
P) 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 intr
acellular pH (pH(i)) and extracellular pH (pH(e)) respectively The NIR
S measurements of the tumour volumes were validated by classic radiola
belling methods using (H2O)-H-3 and [C-14]inulin as markers of total a
nd 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 p
H(e) (P < 0.01), 5-Fluorouracil (5FU) treatment (165 mg kg(-1)) caused
no significant changes in either pH(e) or per cent extracellular volu
me. However significant increases in pH(i) 48 h after treatment (P < 0
.01) correlated with decreased tumour size and improved bioenergetic s
tatus [NTP/inorganic phosphate (P-i) ratio]. This study shows the feas
ibility of an MR method (verified by a 'gold standard') for studying t
he effects of drug treatment on intra- and extracellular spaces and pH
in solid tumours in vivo.