Kavindra Nath1, Elliot C. Woods1, Seung Cheol Lee1, David S. Nelson1, Dennis B. Leeper2, Rong Zhou1, Lin Li1, Jerry D. Glickson1
1Radiology (Molecular Imaging Section),
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.