Intracellular Acidification of Human Melanoma Xenografts by the Respiratory Inhibitor Lonidamine Plus Hyperglycemia: A 31P Magnetic Resonance Spectroscopy Study

Kavindra Nath¹, Elliot C. Woods¹, Seung Cheol Lee¹, David S. Nelson¹, Dennis B. Leeper², Rong Zhou¹, Lin Li¹, Jerry D. Glickson¹

In vivo 31P magnetic resonance spectroscopy illustrates that human melanoma xenografts can be acidified by induction of hyperglycemia combined with administration of lonidamine, an inhibitor of mitochondrial respiration. In melanoma xenograft (10-13 mm diameter), intracellular pH (pHi, measured by chemical shift of the Pi resonance) was reduced by ~0.7 unit during i.v. infusion of glucose (0.6 M) for 120 min along with administration of lonidamine (50 mg/kg). Preliminary result of this study shows that lonidamine combined with hyperglycemia acidified human melanoma xenografts by reducing pHi, a more critical parameter for thermosensitization to improve tumor response to alkylating agents.