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)
| Autor: | M V, Papadopoulou, R, Pouremad, M K, Rao, M, Ji, W D, Bloomer |
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| Rok vydání: | 2001 |
| Předmět: |
Intracellular Fluid
Ovarian Neoplasms Magnetic Resonance Spectroscopy Molecular Structure Imidazoles DNA Fluorine Fibroblasts Cell Fractionation Aerobiosis Cell Hypoxia Cell Line Cricetulus Isotopes Reducing Agents Cricetinae Quinolines Tumor Cells Cultured Animals Humans Female Extracellular Space Lung Protein Binding |
| Zdroj: | In vivo (Athens, Greece). 15(5) |
| ISSN: | 0258-851X |
| Popis: | 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. Uptake studies in V79 cells showed a 5 to 6 fold greater intracellular than extracellular concentration at a range of 100-300 microM input concentrations. A strong sharp peak, which was identified as the parent compound, was observed in the 19F-NMR spectrum of 90% MeCN extracts of V79 cells aerobically exposed to NLTQ-1, indicating that NLTQ-1 was not metabolized under aerobic conditions. Similarly, 19F NMR efflux studies in intact cells showed that the NLTQ-1 was bound to the cells predominantly under hypoxic conditions. 19F-NMR spectra of intact cells, exposed under hypoxic conditions to NLTQ-1, and of their lysates, after precipitation of various cellular components, indicated that possible covalent binding of NLTQ-1 had occurred with macromolecules such as proteins and nucleic acids. Therefore, NLTQ-1 might be suitable as a 19F-MRS/MRI hypoxia probe, although further in vivo work is necessary to verify this matter. |
| Databáze: | OpenAIRE |
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