Novel non-invasive probes for measuring tumor-hypoxia by 19F-magnetic resonance spectroscopy (19F-MRS). Studies in the SCCVII/C3H murine model.

Background: 19F-labeled 2-nitroimidazoles bound to hypoxic cells in tumors are known to be useful probes for measuring hypoxia since they can allow for their non-invasive detection by 19F nuclear magnetic resonance, provided that they do not lose 19F during their hypoxia-mediated metabolism. Two such compounds, N-(m-trifluoromethylbenzyl)-3-(2-nitro-1-imidazolyl)-propylamine hydrochloride (mTFN-1) and 5,6-dimethyl-4-[3-(2-nitro-1-imidazolyl)-propylamino]-2-trifluoromethylpyrimidine hydrochloride (CF3PM) were selected from a series of analogs, for their in vivo evaluation, based on their high solubility in saline and low toxicity in mice.

Materials And Methods: MRS experiments were performed in anesthetized C3H mice bearing SCCVII tumors in their flanks.

In vitro evaluation of 4-[3-(2-nitro-1-imidazolyl)-propylamino]-7-trifluoromethylquinoline hydrochloride (NLTQ-1), a new bioreductive agent as a hypoxia marker by 19F-magnetic resonance spectroscopy (19F-MRS).

19F-labeled bioreductive drugs bound to hypoxic cells in tumors could be detected by nuclear magnetic resonance, provided that they do not lose 19F during their metabolism. NLTQ-1, a 2-nitroimidazole-linked 7-trifluoromethylquinoline, has been synthesized to furnish this aim. NLTQ-1 demonstrated hypoxic selectivities of 7-10 in various cell-lines, in vitro.

Quantitative 19F NMR study of trifluorothymidine metabolism in rat brain.

Metabolism of trifluorothymidine (TFT) and its transport across the blood-brain barrier (BBB) has been measured quantitatively in rats by fluorine-19 nuclear magnetic resonance spectroscopy ((19)F NMR). It is demonstrated that TFT crosses the BBB in micromolar quantities and is metabolized in brain tissue primarily to its free base trifluoromethyluracil (TFMU) by the enzyme thymidine phosphorylase (TP). It is further proposed that the rate of TFMU production can be used as a measure of cerebral TP.

Cerebral metabolism of fluorodeoxyglucose measured with 19F NMR spectroscopy.

Brain extracts from rats given various doses of 2-fluoro-2-deoxy-D-glucose ranging from 20 to 300 mg/kg were examined with 19F NMR spectroscopy for fluorinated metabolic products and compared with the in vivo 19F spectra. Based on the analysis of these spectra and comparison with synthetic reference compounds, 2-fluoro-2-deoxy-D-glucose 6-phosphate and 2-fluoro-2-deoxy-D-mannose 6-phosphate were identified as the major metabolites present. 2-Fluoro-2-deoxy-D-6-phosphogluconate was detected only at high doses of 2-fluoro-2-deoxy-D-glucose administered, along with non-phosphorylated 2-fluoro-2-deoxy-D-glucose and 2-fluoro-2-deoxy-D-mannose.