An assessment of 31P MRS as a method of measuring pH in rat tumours

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Abstract
The contribution of extracellular components to the measurement of pHMRS 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 Pi was between 2.6 and 12.5 μmol/g wet wt depending on tumour type, and of this 53±4.8% (mean ± SEM) was MRS‐visible. The Pi 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 3H2O and [14C]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 Pi(MRS) signal was derived from intracellular Pi, and thus that pHMRS is a measure of pHi. For each tumour type, pHMRS was measured both in “pulse‐acquire” mode at 1.9T 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 pHMRS 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 pHi when calculated from the distribution of lactate across the plasma membrane ([lactate−]out/[lactate−]in = [H+]in/[H+]out) by 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.