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Nuclear Medicine Research Laboratory, Memorial Sloan-Kettering Cancer Center [S. F-D., A. S. G., K. C. R., E. N.], and the Departments of Biochemistry and Neurology, Cornell University Medical College [A. J. L. C.], New York, New York 10021
In vivo studies with L-[13N]glutamate in the Walker 256 carcinosarcoma implanted under the renal capsule of female Sprague-Dawley rats demonstrate that uptake of glutamate and the rate of incorporation of the nitrogen label from this amino acid into metabolites is slower in the tumor than in nontumorous kidney tissue. Glutamate dehydrogenase, glutaminase, and alanine aminotransferase activities are significantly lower within the tumor than within the adjoining kidney. However, the tumor expresses high levels of aspartate aminotransferase, attesting to the importance of this enzyme in the metabolism of glutamate. Indeed, high performance liquid chromatographic analysis showed that the principal metabolic fate of label derived from L-[13N]glutamate in the tumor is incorporation into aspartate. Measurement of specific activity ratios of glutamate to aspartate shows that the transfer of nitrogen from glutamate to aspartate is rapid and that equilibration of label among components of the aspartate aminotransferase reaction is attained within minutes after tumor uptake. Analyses of the nontumorous portion of the implanted kidney also showed that aspartate is the major recipient of glutamate nitrogen. However, high performance liquid chromatographic analyses of deproteinized tissue revealed that glutamine and ammonia are also significant 13N-labeled metabolites formed from L-[13N]glutamate within the kidney. Proportionately lower amounts of these labeled metabolites were found in the tumor.
1 This work was supported in part by NIH Grants CA-34603 and DK-16739 and by Department of Energy Grant DE-FG-02-86-ER-60407. Presented in part at the 34th Annual Meeting of the Society of Nuclear Medicine, June 25, 1987, Toronto, Ontario, Canada.
2 To whom requests for reprints should be addressed, at Nuclear Medicine Research Laboratory, Memorial Sloan-Kettering Cancer Center, 1275 York Avenue, New York, NY 10021.
3 Present address: PET/Cyclotron Facility, University of Michigan, Ann Arbor, MI 48108.
4 Present address: Department of Neoplastic Diseases, Mount Sinai Medical Center, New York, NY 10029.
Received 1/ 4/90.
Revised 4/24/90.
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