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In Vivo ¹⁴N Nuclear Magnetic Resonance Spectroscopy of Tumors: Detection of Ammonium and Trimethylamine Metabolites in the Murine Radiation Induced Fibrosarcoma 1¹

Department of Radiology and Radiological Science, Division of NMR Research, The Johns Hopkins University School of Medicine, Baltimore, Maryland 21205 [M. P. G., J. D. G.], and Department of Radiology, Frederik Philips NMR Research Center, Emory University School of Medicine, Atlanta, Georgia 30322 [I. C.]

The in vivo ¹⁴N nuclear magnetic resonance spectra of s.c. implanted murine radiation induced fibrosarcomas (RIF-1) display narrow resonances assignable to betaine and other trimethylamines and broad resonances due to amino acids and peptides. In 19 of the 41 tumors studied a distinct resonance from the ammonium ion is detectable. The accumulation of ammonium in the tumor to nuclear magnetic resonance detectable levels may result from glutaminolysis (a possible pathway for energy production in the tumor), from the degradation of peptides and proteins, or from the deamination of adenine nucleotides. Estimates of the tissue ammonium concentration were obtained from the in vivo tumor spectrum and the spectrum of the nonlabile trimethylamines in the perchloric acid extract. In the extract, the ¹⁴N resonances of betaine, carnitine, choline, phosphorylcholine, and glycerophosphorylcholine were resolved, and a relatively high level of tissue urea was observed. Spin-lattice relaxation times were obtained for the ¹⁴N nucleus of each of these metabolites in phosphate buffer.

¹ This research was supported by an Institutional Research Grant from The Johns Hopkins University School of Medicine (M. P. G.) and USPHS Grant CA44703 from the NIH (J. D. G.).

² To whom requests for reprints should be addressed.

Received 12/12/90. Accepted 4/22/91.