A study is proposed to develop in vivo 31P NMR methods for noninvasively monitoring the metabolism of murine tumors and to determine if changes in concentrations of phosphorous metabolites can be detected in tumors responding to chemotherapy. The investigation will serve as a basis for development of noninvasive NMR techniques for monitoring tumor metabolism and response to therapy in humans. Two model tumors have been chosen for this study -- MOPC 104E myeloma in BALB/c mice and the Dunn osteosarcoma in C3H/HEJ mice. The total body burden of tumor cells will be assayed by the blood level of tumor specific anti-Dextran IgM (MOPC 104E myeloma) or alkaline phosphatase (osteosarcoma). Concentrations of ATP, ADP, pyridine dinucleotides, inorganic phosphate (Pi), phosphocreatine (PCr) and sugar phosphates will be measured in both untreated tumors and tumors subjected to chemotherapy (with BCNU). The pH of the tumor will be measured from the chemical shift of Pi. Attempts will be made to correlate the levels of specific phosphorous metabolites with the extent of cell-kill, with the extent of hypoxia, and with the susceptibility of the tumors to chemotherapy.
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