AN ASSESSMENT OF P-31 MRS AS A METHOD OF MEASURING PH IN RAT-TUMORS

The contribution of extracellular components to the measurement of pH(MRS) of a variety of rat tumours (nitrosomethyl urea induced mammary tumours, GH3 prolactinomas, Hepatoma 9618a, UA hepatomas and Walker sarcomas) has been assessed. Acid extractable P(i) was between 2.6 and 12.5 mumol/g wet wt depending on tumour type, and of this 53 +/- 4.8% (mean +/- SEM) was MRS-visible. The P(i) content of tumour exudate was 2-3 mM, of interstitial fluid (sampled from a micropore chamber incorporated within a tumour) 1.7 mm, and of blood plasma 1.95 mm. The mean extracellular volumes of the tumours, measured by distribution of (H2O)-H-3 and [C-14]inulin, were 49-55% depending on tumour type and were at least twice that found in normal liver. Calculations suggested that for most tumours with an extracellular volume not exceeding 55%, at least 65% of the P(i(MRS)) signal was derived from intracellular P(i), and thus that pH(MRS) is a measure of pH(i). For each tumour type, pH(MRS) was measured both in 'pulse-acquire' mode at 1.9 T which may include signals from surrounding tissue, and in localized mode at 4.7 T where the signal came uniquely from tumour tissue. The steady state pH(MRS) was either neutral or on the alkaline side of neutrality (pH range 7.04-7.37). Raised lactate content and decreased buffering capacity (compared to normal tissues) accompanied these neutral to alkaline pH values. The extracellular pH of all the tumour types was found to be significantly lower than pH(i) when calculated from the distribution of lactate across the plasma membrane ([lactate-]out/[lactate-]in = [H+]in/[H+]out) the method of Veech [Veech, R. L. NMR Biomed. 4, 53-58 (1991)] whereas in control tissue (liver) the extracellular pH was higher, as would be expected.