METABOLISM OF N-13 AMMONIA AND L-AMINO ACIDS IN TUMORS

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The goal of this research is to use the cyclotron-produced, short-lived radionuclide nitrogen-13 to study the in vivo metabolism of labeled L-amino acids and ammonia in murine tumors which are sensitive or resistant to glutaminase or asparaginase therapy. The metabolites of these N-13 labeled radiopharmaceuticals in blood and tumor homogenates will be determined using reverse phase and ion exchange chromatographic analyses. Tissue distribution studies using N-13 ammonia and L-(amide-N-13) glutamine have been performed in control and glutaminase 7A treated Sarcoma-180 (glutaminase sensitive) and Ridgeway Osteogenic Sarcoma (glutaminase resistant) mice. There do not appear to be any significant differences in the tissue distributions of N-13 ammonia or glutamine between the glutaminase-treated and control mice. Metabolic fate studies have been performed on tumor and blood homogenates 1, 5, and 10 min after either N-13 ammonia or N-13 glutamine administration in treated glutaminase-sensitive and -resistant tumor-bearing mice. The metabolic fate of the N-13 label after administration of either agent is primarily N-13 urea with the concentration increasing with time with smaller amounts in the acidic metabolites and in acidic amino acids. No labeled urea (only an unknown co-eluant) was formed during in vitro studies in which S-180 tumor slices were incubated with N-13 ammonia, suggesting that the N-13 urea formed in the tumor in the in vivo studies was not due to de novo synthesis in the tumor. Metabolic fate studies performed to date on Sarcoma-180 tumor and blood homogenates in glutaminase-treated animals after N-13 ammonia injection do not appear to be significantly different from untreated animals. (B)