HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Rasey, J. S. Articles by Tewson, T. J. Search for Related Content PubMed PubMed Citation Articles by Rasey, J. S. Articles by Tewson, T. J.

Characterization of [¹⁸F]Fluoroetanidazole, a New Radiopharmaceutical for Detecting Tumor Hypoxia

Departments of Radiation Oncology and Radiology, University of Washington School of Medicine, Seattle, Washington

Correspondence: For correspondence or reprints contact: Janet S. Rasey, PhD, Radiation Oncology, University of Washington, Box 356069, Seattle, WA 98195.

ABSTRACT

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 (130–430mg). 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 (700–5100 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.

Key Words: hypoxia • [¹⁸F]fluoroetanidazole • tumor imaging • [¹⁸F]fluoromisonidazole

This article has been cited by other articles:

				K. A. Krohn, J. M. Link, and R. P. Mason Molecular Imaging of Hypoxia J. Nucl. Med., June 1, 2008; 49(Suppl_2): 129S - 148S. [Abstract] [Full Text] [PDF]

				M. Takasawa, R. R. Moustafa, and J.-C. Baron Applications of Nitroimidazole In Vivo Hypoxia Imaging in Ischemic Stroke Stroke, May 1, 2008; 39(5): 1629 - 1637. [Abstract] [Full Text] [PDF]

				S. Sobhanifar, C. Aquino-Parsons, E. J. Stanbridge, and P. Olive Reduced Expression of Hypoxia-Inducible Factor-1{alpha} in Perinecrotic Regions of Solid Tumors Cancer Res., August 15, 2005; 65(16): 7259 - 7266. [Abstract] [Full Text] [PDF]

				M. Piert, H.-J. Machulla, M. Picchio, G. Reischl, S. Ziegler, P. Kumar, H.-J. Wester, R. Beck, A. J.B. McEwan, L. I. Wiebe, et al. Hypoxia-Specific Tumor Imaging with 18F-Fluoroazomycin Arabinoside J. Nucl. Med., January 1, 2005; 46(1): 106 - 113. [Abstract] [Full Text] [PDF]

				M. Bruehlmeier, U. Roelcke, P. A. Schubiger, and S. M. Ametamey Assessment of Hypoxia and Perfusion in Human Brain Tumors Using PET with 18F-Fluoromisonidazole and 15O-H2O J. Nucl. Med., November 1, 2004; 45(11): 1851 - 1859. [Abstract] [Full Text] [PDF]

				J. G. Rajendran, D. A. Mankoff, F. O'Sullivan, L. M. Peterson, D. L. Schwartz, E. U. Conrad, A. M. Spence, M. Muzi, D. G. Farwell, and K. A. Krohn Hypoxia and Glucose Metabolism in Malignant Tumors: Evaluation by [18F]Fluoromisonidazole and [18F]Fluorodeoxyglucose Positron Emission Tomography Imaging Clin. Cancer Res., April 1, 2004; 10(7): 2245 - 2252. [Abstract] [Full Text] [PDF]

				T. Kaneta, Y. Takai, Y. Kagaya, Y. Yamane, H. Wada, M. Yuki, R. Iwata, M. Tsujitani, S. Takahashi, and S. Yamada Imaging of Ischemic but Viable Myocardium Using a New 18F-Labeled 2-Nitroimidazole Analog, 18F-FRP170 J. Nucl. Med., January 1, 2002; 43(1): 109 - 116. [Abstract] [Full Text] [PDF]

				T. Gronroos, O. Eskola, K. Lehtio, H. Minn, P. Marjamaki, J. Bergman, M. Haaparanta, S. Forsback, and O. Solin Pharmacokinetics of [18F]FETNIM: A Potential Hypoxia Marker for PET J. Nucl. Med., September 1, 2001; 42(9): 1397 - 1404. [Abstract] [Full Text] [PDF]