Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:3.5.4.1 (cytosine deaminase)
 747 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Fluorine-19 nuclear magnetic resonance (19F NMR) spectroscopy provides a highly specific tool for identifying fluorine-containing drugs and their metabolites in biological media. This article focuses on the application of 19F NMR to the metabolic studies of fluoropyrimidine drugs in clinical use. The value and difficulties encountered in investigations on drug metabolism are first discussed. The metabolism and disposition studies of the anticancer drug 5-fluorouracil, the mainstay of antimetabolite treatment for solid tumors, and its prodrugs, doxifluridine and capecitabine, are then extensively reviewed. The studies dealing with the antimycotic agent, 5-fluorocytosine, as well as the novel anticancer drug, gemcitabine, are also considered. From in vitro (biofluids or tissue extracts) 19F NMR analysis, seven new metabolites of 5-fluorouracil, doxifluridine, capecitabine and 5-fluorocytosine were identified. Except two, they were only detected using this technique. This emphasizes the high analytical potential of in vitro 19F NMR. In vivo 19F NMR is non-invasive and thus allows the quantitative monitoring of the metabolism of 5-fluorouracil in the target tissue, e.g. the tumor, as well as its biodistribution. Another promising application is its ability to estimate the level of yeast cytosine deaminase gene expression in human tumors from the quantitative monitoring of 5-fluorouracil formation from the non-cytotoxic drug 5-fluorocytosine. Notwithstanding these successes, the limited sensitivity and spectral resolution of 19F NMR precludes its extensive applicability to all the fluorinated drugs.
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PMID:Fluorine nuclear magnetic resonance, a privileged tool for metabolic studies of fluoropyrimidine drugs. 1146 49

The aim of this study was to evaluate the applicability of fluorine-19 magnetic resonance spectroscopy ((19)F MRS) for monitoring in vivo the conversion of 5-fluorocytosine (5-FC) to 5-fluorouracil (5-FU) after using an attenuated Salmonella Typhimurium strain recombinant to provide cytosine deaminase (TAPET-CD). The (19)F MRS measurements were done on mice bearing the human colon tumour xenograft (HCT116). The intratumoural conversion is greater when TAPET-CD/5-FC is delivered intratumourally (i.tu.) than when TAPET-CD is delivered intravenously (i.v.) and 5-FC intraperitoneally (i.p.). Repeat measurements of the same tumour also yielded important information on the tumour colonization by TAPET-CD through the correlated 5-FC to 5-FU conversion efficacy. The in vivo MRS spectra were confirmed by in vitro (19)F MRS of perchloric acid extracts of the tumour tissue. No 5-FU metabolites were detectable in vivo in the tumours. However, the in vitro measurements revealed, besides 5-FC and 5-FU, the presence of small amounts of catabolites. Finally, spectra obtained in vitro from liver extracts of tumour-bearing mice treated i.tu. with TAPET-CD/5-FC showed no 5-FU and only little amounts of catabolites. Our data illustrate most importantly the potential of (19)F MRS to monitor biologically-based treatments involving cytosine deaminase.
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PMID:Non-invasive 19F MR spectroscopy of 5-fluorocytosine to 5-fluorouracil conversion by recombinant Salmonella in tumours. 1458 86