Abstract #0058

Lonidamine Reverses the Cell Membrane PH Gradient of Human DB-1 Melanoma Xenografts

Kavindra Nath¹, David Nelson¹, Andrew Ho¹, Moses Darpolor¹, Stephen Pickup¹, Rong Zhou¹, Daniel Heitjan², Deenis Leeper³, Jerry Glickson¹

¹Radiology, University of Pennsylvania, Philadelphia, PA, United States; ²Biostatistics and Epidemiology, University of Pennsylvania, Philadelphia, PA, United States; ³Radiation Oncology, Thomas Jefferson University, Philadelphia, PA, United States

Synopsis: Tumors generally have an acidic extracellular pH (pHe) and a neutral to alkaline intracellular pH (pHi), whereas normal cells generally exhibit neutral intracellular and extracellular environments. Here we demonstrate by 31P MRS that the administration of lonidamine (100 mg/kg, i.p.) reverses the pH gradient of human DB-1 melanoma xenografts in nude mice: pHe going from 7.00 0.04 to 6.80 0.07 (p = 0.085) while pHi goes from 6.90 0.05 to 6.40 0.10 (p < 0.001). Selective tumor acidification makes the tumor much more susceptible to systemic chemotherapy with nitrogen mustards.