The objectives of the proposed research are to determine the specificity and selectivity of in-vivo accumulation of nitrogen-13 derived from intravenously-administered labeled L-amino acids in those primary and metastatic human tumors associated with aberrant amino acid metabolism (melanoma and neuroblastoma and tumors with glutamine requirements), to explore the use of these radiopharmaceuticals for monitoring the progress of drug or radiation therapy in cancer patients and to investigate the mechanisms of label concentration and metabolism of these agents in animal tumors as a means of understanding their fate in human cancer. The proposed clinical studies will employ quantitative external scintigraphic measurements of tumor 13N concentration in order to compare the efficacy of these radiolabeled amino acids for imaging untreated tumors and to assess changes in label accumulation on repeat studies during the course of treatment. The animal studies wil employ excision and radioassay of tumor tissue in addition to imaging procedures and the determination of the metabolic fate of the 13N label derived from these radiopharmaceuticals by means of ion exchange and reverse phase high pressure liquid chromatography and enzymatic assay. It is also proposed to develop methods applicable to humans for the measurement of tumor blood flow by external scintigraphy, including the use of position emission tomography.
