Kavindra Nath1, David S. Nelson1,
Andrew Ho1, Brian P. Weiser2, Rong Zhou1,
Stephen Pickup1, Lin Z. J. Li1, Deenis Leeper3,
Jerry D. Glickson1
1Radiology, University of
Pennsylvania, Philadelphia, PA, United States; 2Pharmacology,
University of Pennsylvania, Philadelphia, PA, United States; 3Radiation
Oncology, Thomas Jefferson University, Philadelphia, PA, United States
Synopsis: In vivo P-31MRS was used to monitor the effects of lonidamine on pH and bioenergetics of human melanoma xenografts and normal tissues. Intracellular pH was reduced through 180 minutes with a maximum decrease (0.6 units, p=0.003) occurring 80 min. after lonidamine injection, and the bioenergetics (βNTP/Pi ratio) of the tumor decreased relative to baseline (56%, p=0.004). In liver, a transient decrease in pH (~0.2 units, p=0.19) was observed after 20 mins, with a maximum decrease in βNTP/Pi (~21%, p=0.04) occurring after 40 min. Noninvasive monitoring of brain and muscle showed no significant changes. This selective decrease of tumor pH and bioenergetics may be exploited for sensitization to pH dependent chemotherapy.