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).

Abstract

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.

• Authors: M V Papadopoulou, R Pouremad, M K Rao, M Ji, W D Bloomer
• Journal: In vivo (Athens, Greece) (In Vivo) 2001 Sep-Oct Vol. 15 Issue 5 Pg. 365-71 ISSN: 0258-851X [Print] Greece
• PMID: 11695231 (Publication Type: Journal Article)

Chemical References

• 4-(3-(2-nitro-1-imidazolyl)-propylamino)-7-trifluoromethylquinoline hydrochloride
• Imidazoles
• Isotopes
• Quinolines
• Reducing Agents
• Fluorine
• DNA

Topics

• Aerobiosis
• Animals
• Cell Fractionation
• Cell Hypoxia
• Cell Line (chemistry, drug effects)
• Cricetinae
• Cricetulus
• DNA (metabolism)
• Extracellular Space (chemistry)
• Female
• Fibroblasts (chemistry, drug effects)
• Fluorine (analysis)
• Humans
• Imidazoles (analysis, chemistry, metabolism, toxicity)
• Intracellular Fluid (chemistry)
• Isotopes (analysis)
• Lung (cytology)
• Magnetic Resonance Spectroscopy
• Molecular Structure
• Ovarian Neoplasms (pathology)
• Protein Binding
• Quinolines (analysis, chemistry, metabolism, toxicity)
• Reducing Agents (analysis, chemistry, metabolism, toxicity)
• Tumor Cells, Cultured (chemistry, drug effects)