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Abstract #0058

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

MAGNA25Kavindra 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.

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Keywords

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