The relationship between intracellular and extracellular pH in spontaneouscanine tumors

Recently, it has been suggested that the cellular uptake of chemotherapeuti c drugs may be dependent on the pH gradient between the intracellular (pH(i )) and extracellular (pH(e)) compartments. It has been demonstrated in muri ne tumor models that the extracellular environment is acidic, relative to t he intracellular environment, thus favoring preferential accumulation of dr ugs that are weak acids into cells. However, concomitant measurements of pH (i) and pH(e) in spontaneous tumors have not been reported, so it is not ce rtain how well the murine results translate to the clinical scenario. In th is study, both types of measurements were performed in dogs with spontaneou s malignant soft tissue tumors, On average, pH(e) was more acidic than pH(i ), with maintenance of a more physiologically balanced intracellular tumor environment. However, the magnitude of the gradient varied widely, and indi vidual tumors had both positive and negative pH gradients (pH(i) - pH(e)). These data suggest that the magnitude and direction of the pH gradient mag need to be measured for individual patient tumors and/or that manipulation of pH(e) may be required if exploitation of the pH gradient is to be achiev ed for tumor-selective augmentation of intracellular drug delivery.