The objectives of the proposed research are to contribute to the management of cancer patients by using nitrogren-13 labeled amino acids as imaging agents for assessment of tumor function and functional response to therapy and to obtain a better understanding of in vivo tumor metabolism by study of N-13 L- amino acids. We shall study the selectivity of in vivo concentration of N-13 derived for intravenously administered L(n-13) tyrosine in human tumors with aberrant aromatic amino acid metabolism such as malignant melanoma and neuroblastoma by scintigraphic measurements. The specificity of label accumulation from tyrosine will be determined by sequential studies with L-(N-13) glutamate. L-(amideN-13) Glutamine will be evaluated in comparison with L-(N-13) glutamate for scintigraphic measurement of soft tissue sarcoma tumor response to therapy in paired, same session studies. The efficacy of L-(amide-N-13) glutamine as an imaging agent of detecting extrahepatic colorectal metastases shall be determined. The mechanisms of localization and the metabolic fate of the labeled amino acid shall be studied in transplanted rodent tumors as a means of interpreting cancer in humans. The animal studies will employ imaging procedures as well as dissection of tumors and analyses of extracts utilizing high performance liquid chromatography and analyses of extracts utilizing high performance liquid chromatography and analyses of radioactive peaks by chemical and enzymatic techiques. Concurrent studies will be carried out with N-13 and C-14 labeled L-glutamine and glutamate to study the fate of the carbon skeleton of the amino acids and to determine its role as an energy source for tumors.

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Research Project (R01)
Project #
5R01CA034603-05
Application #
3172338
Study Section
Diagnostic Radiology Study Section (RNM)
Project Start
1983-12-01
Project End
1989-11-30
Budget Start
1987-12-01
Budget End
1988-11-30
Support Year
5
Fiscal Year
1988
Total Cost
Indirect Cost
Name
Sloan-Kettering Institute for Cancer Research
Department
Type
DUNS #
064931884
City
New York
State
NY
Country
United States
Zip Code
10065
Filc-DeRicco, S; Gelbard, A S; Cooper, A J et al. (1990) Short-term metabolic fate of L-[13N]glutamate in the Walker 256 carcinosarcoma in vivo. Cancer Res 50:4839-44
Gelbard, A S; Cooper, A J; Asano, Y et al. (1990) Methods for the enzymatic synthesis of tyrosine and phenylalanine labeled with nitrogen-13. Int J Rad Appl Instrum A 41:229-33
Cooper, A J; Nieves, E; Rosenspire, K C et al. (1988) Short-term metabolic fate of 13N-labeled glutamate, alanine, and glutamine(amide) in rat liver. J Biol Chem 263:12268-73
Cooper, A J; Nieves, E; Coleman, A E et al. (1987) Short-term metabolic fate of [13N]ammonia in rat liver in vivo. J Biol Chem 262:1073-80
Nieves, E; Rosenspire, K C; Filc-DeRicco, S et al. (1986) High-performance liquid chromatographic on-line flow-through radioactivity detector system for analyzing amino acids and metabolites labeled with nitrogen-13. J Chromatogr 383:325-37
Gelbard, A S; Kaseman, D S; Rosenspire, K C et al. (1985) Enzymatic syntheses of carbamyl phosphate, L-citrulline, and N-carbamyl L-aspartate labeled with either 13N or 11C. Int J Nucl Med Biol 12:235-42