Abstract | UNLABELLED: 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.
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Authors | J S Rasey, P D Hofstrand, L K Chin, T J Tewson |
Journal | Journal 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 |
PMID | 10452326
(Publication Type: Journal Article, Research Support, U.S. Gov't, P.H.S.)
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Chemical References |
- Contrast Media
- Fluorine Radioisotopes
- Radiopharmaceuticals
- fluoroetanidazole
- fluoromisonidazole
- Etanidazole
- Misonidazole
- Oxygen
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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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