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The Relationship between Intracellular and Extracellular pH in Spontaneous Canine Tumors¹

Departments of Radiation Oncology [D. M. P., J. M. P., Z. V., M. W. D.] and Radiology [H. C. C.], Duke University Medical Center, Durham, North Carolina 27710, and Departments of Companion Animal and Special Species Medicine [R. L. P.] and Anatomy, Physiological Sciences and Radiology [D. E. T.], North Carolina State University College of Veterinary Medicine, Raleigh, North Carolina 27606

Recently, it has been suggested that the cellular uptake of chemotherapeutic drugs may be dependent on the pH gradient between the intracellular (pH_i) and extracellular (pH_e) compartments. It has been demonstrated in murine tumor models that the extracellular environment is acidic, relative to the intracellular environment, thus favoring preferential accumulation of drugs 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 certain how well the murine results translate to the clinical scenario. In this study, both types of measurements were performed in dogs with spontaneous 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 individual tumors had both positive and negative pH gradients (pH_i - pH_e). These data suggest that the magnitude and direction of the pH gradient may 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 achieved for tumor-selective augmentation of intracellular drug delivery.

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