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Characterization of [18F]fluoroetanidazole, a new radiopharmaceutical for detecting tumor hypoxia.

AbstractUNLABELLED:
Fluorinated derivatives of etanidazole are being explored as probes for tumor hypoxia. Our research group has synthesized [18F]fluoroetanidazole (FETA) and now reports the oxygen dependency of binding to cells in vitro, the biodistribution of the tracer in tumor-bearing mice and the analysis of metabolites in their plasma and urine.
METHODS:
Four cultured rodent cell lines (V79, 36B10, EMT6 and RIF1) were incubated with [18F]FETA for various times under graded O2 concentrations. We also compared the biodistributions of [18F]FETA and [18F]fluoromisonidazole (FMISO) at 2 and 4 h postinjection in C3H mice bearing KHTn tumors (130-430 mg). Reverse-phase high-performance liquid chromatography was used to distinguish metabolites from parent drugs in urine and plasma of mice injected with [18F]FETA or [18F]FMISO.
RESULTS:
In cells labeled in vitro, O2 levels of 600-1300 ppm inhibited binding by 50% relative to uptake under anoxic conditions (<10 ppm). These inhibitory values are not statistically different from those reported for [18F]FMISO in the same cell lines (700-1500 ppm). In the biodistribution studies, uptake in heart, intestine, kidney and tumor was similar for both tracers 4 h after injection, whereas retention of [18F]FETA in liver and lung was significantly lower. Less uptake of [18F]FETA in liver suggests that this nitroimidazole is metabolized less than [18F]FMISO. The brain-to-blood ratios indicate that [18F]FETA readily crosses the blood-brain barrier. High-performance liquid chromatography of urine demonstrated that 10% of [18F]FETA-derived activity was in metabolites at 2 h postinjection, with 15% in metabolites by 4 h; comparable values for [18F]FMISO were 36% and 57%, respectively.
CONCLUSION:
We conclude from these data that [18F]FETA holds promise as a new hypoxia tracer in patients, having oxygen dependency of binding similar to [18F]FMISO in vitro and displaying less retention in liver and fewer metabolites in vivo.
AuthorsJ S Rasey, P D Hofstrand, L K Chin, T J Tewson
JournalJournal of nuclear medicine : official publication, Society of Nuclear Medicine (J Nucl Med) Vol. 40 Issue 6 Pg. 1072-9 (Jun 1999) ISSN: 0161-5505 [Print] United States
PMID10452326 (Publication Type: Journal Article, Research Support, U.S. Gov't, P.H.S.)
Chemical References
  • Contrast Media
  • Fluorine Radioisotopes
  • Radiopharmaceuticals
  • fluoroetanidazole
  • fluoromisonidazole
  • Etanidazole
  • Misonidazole
  • Oxygen
Topics
  • Animals
  • Binding Sites
  • Blood-Brain Barrier
  • Cell Hypoxia
  • Chromatography, High Pressure Liquid
  • Contrast Media
  • Cricetinae
  • Cricetulus
  • Etanidazole (analogs & derivatives, pharmacokinetics)
  • Female
  • Fibroblasts (metabolism)
  • Fibrosarcoma (diagnostic imaging, metabolism)
  • Fluorine Radioisotopes (pharmacokinetics)
  • Glioma (diagnostic imaging, metabolism)
  • Lung (cytology, metabolism)
  • Male
  • Mammary Neoplasms, Experimental (diagnostic imaging, metabolism)
  • Mice
  • Mice, Inbred C3H
  • Misonidazole (analogs & derivatives, pharmacokinetics)
  • Neoplasms, Experimental (diagnostic imaging, metabolism)
  • Oxygen (metabolism)
  • Radionuclide Imaging
  • Radiopharmaceuticals (pharmacokinetics)
  • Rats
  • Sarcoma, Experimental (diagnostic imaging, metabolism)
  • Time Factors
  • Tissue Distribution
  • Tumor Cells, Cultured

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