The metabolism of
glycine into
glutathione was monitored noninvasively in vivo in intact rat mammary
adenocarcinomas (R3230Ac) by MRI and MRS. Metabolism was tracked by following the
isotope label from intravenously infused [2-(13)C]-
glycine into the glycinyl residue of
glutathione. Signals from [2-(13)C]-
glycine and γ-glutamylcysteinyl-[2-(13)C]-
glycine ((13)C-glutathione) were detected by nonlocalized (13)C spectroscopy, as these resonances are distinct from background signals. In addition, using spectroscopic imaging methods, heterogeneity in the in vivo
tumor distribution of
glutathione was observed. In vivo spectroscopy also detected
isotope incorporation from [2-(13)C]-
glycine into both the 2- and 3-carbons of
serine. Analyses of
tumor tissue extracts showed single- and multiple-label incorporation from [2-(13)C]-
glycine into
serine from metabolism through the
serine hydroxymethyltransferase and
glycine cleavage system pathways. Mass spectrometric analysis of extracts also showed that
isotope-labeled
serine is further metabolized via the trans-sulfuration pathway, as (13)C
isotope labels appear in both the glycinyl and cysteinyl residues of
glutathione. Our studies demonstrate the use of MRI and MRS for the monitoring of
tumor metabolic processes central to oxidative stress defense.