Characterization of [F-18]fluoroetanidazole, a new radiopharmaceutical fordetecting tumor hypoxia

Fluorinated derivatives of etanidazole are being explored as probes for tum or hypoxia. Our research group has synthesized [F-18]fluoroetanidazole (FET A) 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 met abolites in their plasma and urine. Methods: Four cultured rodent cell line s (V79, 36B10, EMT6 and RIF1) were incubated with [F-18]FETA for various ti mes under graded O-2 concentrations. We also compared the biodistributions of [F-18]FETA and [F-18]fluoromisonidazole (FMISO) at 2 and 4 h postinjecti on in C3H mice bearing KHTn tumors (130-430 mg). Reverse-phase high-perform ance liquid chromatography was used to distinguish metabolites from parent drugs in urine and plasma of mice injected with [F-18]FETA or [F-18]FMISO. Results: In cells labeled in vitro, O-2 levels of 600-1300 ppm inhibited bi nding by 50% relative to uptake under anoxic conditions (<10 ppm). These in hibitory values are not statistically different from those reported for [F- 18]FMISO in the same cell lines (700-1500 ppm). Int he biodistribution Stud ies, uptake in heart, intestine, kidney and tumor was similar for both trac ers 4 h after injection, whereas retention of [F-18]FETA in liver and lung was significantly lower. Less uptake of [F-18]FETA in liver suggests that t his nitroimidazole is metabolized less than [F-18]FMISO. The brain-to-blood ratios indicate that [F-18]FETA. readily crosses the blood-brain barrier. High-performance liquid chromatography of urine demonstrated that 10% of [F -18]FETA-derived activity was in metabolites at 2 h postinjection, with 15% in metabolites by 4 h; comparable values for [F-18]FMISO were. 36% and 57% , respectively. Conclusion: We conclude from these data that [F-18]FETA hol ds promise as a new hypoxia tracer in patients, having oxygen dependency of binding similar to [F-18]FMISO in vitro and displaying less retention in l iver and fewer metabolites in vivo.