(31) P and (1) H MRS of DB-1 melanoma xenografts: lonidamine selectively decreases tumor intracellular pH and energy status and sensitizes tumors to melphalan.

摘要: In vivo (31) P MRS demonstrates that human melanoma xenografts in immunosuppressed mice treated with lonidamine (LND, 100 mg/kg intraperitoneally) exhibit a decrease intracellular pH (pH(i) ) from 6.90 ± 0.05 to 6.33 0.10 (p 0.05) and monotonic decline bioenergetics (nucleoside triphosphate/inorganic phosphate) of 66.8 5.7% at 20 min post-LND, no significant change pH(e) small transient (32.9 10.6%, p > 40 post-LND. No changes pH(i) or adenosine phosphate were detected the brain , bioenergetics; 0.1) skeletal muscle for least 120 Steady-state tumor lactate monitored by (1) H selective multiquantum pulse sequence Hadamard localization increased approximately three-fold = 0.009). Treatment LND systemic response melphalan (LPAM; 7.5 intravenously), producing growth delay 19.9 2.0 days (tumor doubling time, 6.15 0.31 days; log(10) cell kill, 0.975 0.110; 89.4 2.2%) compared alone 1.1 0.1 LPAM 4.0 0.0 days. The study effects on may sensitize pH-dependent therapeutics, such as chemotherapy alkylating agents hyperthermia.