In vivo Measurement of Regional Brain and Tumor pH Using [ 14 C]Dimethyloxazolidinedione and Quantitative Autoradiography. II: Characterization of the Extracellular Fluid Compartment Using pH-Sensitive Microelectrodes and [ 14 C]Sucrose

We measured the extracellular (interstitial) pH (pH_e) of RG-2 rat gliomas using H⁺-sensitive microelectrodes and estimated the volume of tumor extracellular space based on the tissue-plasma ratio of [¹⁴C]sucrose. The average RG-2 pH_e was 7.63 ± 0.15 (mean ± SD, n = 6), whereas the average pH_e of contralateral brain tissue was 7.34 ± 0.10 (n = 3) and arterial pH was 7.36 ± 0.02. RG-2 extracellular space water volume was estimated to be 0.3 ml water/g tissue. In separate experiments in normal, nontumored rats, intracellular pH (pH_i) was calculated for nine gray and white matter regions based on measurements of tissue and plasma [¹⁴C]dimethyloxazolidinedione concentration. pH_i values ranged from 6.80 to 6.94, and no consistent gray–white differences were observed. Our data suggest that tumor pH_i is not more acidic than that of normal brain tissue and that the observed alkalinity of primary brain tumors is due to the presence of a large alkaline extracellular space.