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

This Article Figures Only Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Related articles in JNM 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 Tipre, D. N. Articles by Pike, V. W. Search for Related Content PubMed PubMed Citation Articles by Tipre, D. N. Articles by Pike, V. W.

PET Imaging of Brain 5-HT_1A Receptors in Rat In Vivo with ¹⁸F-FCWAY and Improvement by Successful Inhibition of Radioligand Defluorination with Miconazole

¹ Molecular Imaging Branch, National Institute of Mental Health, National Institutes of Health, Bethesda, Maryland; ² Trident Imaging, Inc., Rockville, Maryland; and ³ Imaging Physics Laboratory, National Institute for Biomedical Imaging and Bioengineering, National Institutes of Health, Bethesda, Maryland

Correspondence: For correspondence or reprints contact: Dnyanesh N. Tipre, PhD, National Institutes of Health, Bldg. 1, Room B3-10, 1 Center Dr., MSC 0135, Bethesda, MD 20892-0135. E-mail: dnyanesht{at}yahoo.com

¹⁸F-FCWAY (¹⁸F-trans-4-fluoro-N-(2-[4-(2-methoxyphenyl) piperazin-1-yl)ethyl]-N-(2-pyridyl)cyclohexanecarboxamide) is useful in clinical research with PET for measuring serotonin 1A (5-HT_1A) receptor densities in brain regions of human subjects but has significant bone uptake of radioactivity due to defluorination. The uptake of radioactivity in skull compromises the accuracy of measurements of 5-HT_1A receptor densities in adjacent areas of brain because of spillover of radioactivity through the partial-volume effect. Our aim was to demonstrate with a rat model that defluorination of ¹⁸F-FCWAY may be inhibited in vivo to improve its applicability to measuring brain regional 5-HT_1A receptor densities. Methods: PET of rat head after administration of ¹⁸F-FCWAY was used to confirm that the distribution of radioactivity measured in brain is dominated by binding to 5-HT_1A receptors and to reveal the extent of defluorination of ¹⁸F-FCWAY in vivo as represented by radioactivity (¹⁸F-fluoride ion) uptake in skull. Cimetidine, diclofenac, and miconazole, known inhibitors of CYP450 2EI, were tested for the ability to inhibit defluorination of ¹⁸F-FCWAY in rat liver microsomes in vitro. The effects of miconazole treatment of rats on skull radioactivity uptake and, in turn, its spillover on brain 5-HT_1A receptor imaging were assessed by PET with venous blood analysis. Results: PET confirmed the potential of ¹⁸F-FCWAY to act as a radioligand for 5-HT_1A receptors in rat brain and also revealed extensive defluorination. In rat liver microsomes in vitro, defluorination of ¹⁸F-FCWAY was almost completely inhibited by miconazole and, to a less extent, by diclofenac. In PET experiments, treatment of rats with miconazole nitrate (60 mg/kg intravenously) over the 45-min period before administration of ¹⁸F-FCWAY almost obliterated defluorination and bone uptake of radioactivity. Also, brain radioactivity almost doubled while the ratio of radioactivity in receptor-rich ventral hippocampus to that in receptor-poor cerebellum almost tripled to 14. The plasma half-life of radioligand was also extended by miconazole treatment. Conclusion: Miconazole treatment, by eliminating defluorination of ¹⁸F-FCWAY, results in effective imaging of brain 5-HT_1A receptors in rat. ¹⁸F-FCWAY PET in miconazole-treated rats can serve as an effective platform for investigating 5-HT_1A receptors in rodent models of neuropsychiatric conditions or drug action.

Key Words: ¹⁸F-FCWAY • miconazole • defluorination • 5-HT_1A receptors • rat • PET

Related articles in JNM:

This Month in JNM

JNM 2006 47: 7a-8a. [Full Text]  

This article has been cited by other articles:

				H. U. Shetty, S. S. Zoghbi, F. G. Simeon, J.-S. Liow, A. K. Brown, P. Kannan, R. B. Innis, and V. W. Pike Radiodefluorination of 3-Fluoro-5-(2-(2-[18F](fluoromethyl)-thiazol-4-yl)ethynyl)benzonitrile ([18F]SP203), a Radioligand for Imaging Brain Metabotropic Glutamate Subtype-5 Receptors with Positron Emission Tomography, Occurs by Glutathionylation in Rat Brain J. Pharmacol. Exp. Ther., December 1, 2008; 327(3): 727 - 735. [Abstract] [Full Text] [PDF]

				Y. H. Ryu, J.-S. Liow, S. Zoghbi, M. Fujita, J. Collins, D. Tipre, J. Sangare, J. Hong, V. W. Pike, and R. B. Innis Disulfiram Inhibits Defluorination of 18F-FCWAY, Reduces Bone Radioactivity, and Enhances Visualization of Radioligand Binding to Serotonin 5-HT1A Receptors in Human Brain J. Nucl. Med., July 1, 2007; 48(7): 1154 - 1161. [Abstract] [Full Text] [PDF]

				D. E. Ponde, C. S. Dence, N. Oyama, J. Kim, Y.-C. Tai, R. Laforest, B. A. Siegel, and M. J. Welch 18F-Fluoroacetate: A Potential Acetate Analog for Prostate Tumor Imaging--In Vivo Evaluation of 18F-Fluoroacetate Versus 11C-Acetate J. Nucl. Med., March 1, 2007; 48(3): 420 - 428. [Abstract] [Full Text] [PDF]

				N. Saigal, R. Pichika, B. Easwaramoorthy, D. Collins, B. T. Christian, B. Shi, T. K. Narayanan, S. G. Potkin, and J. Mukherjee Synthesis and Biologic Evaluation of a Novel Serotonin 5-HT1A Receptor Radioligand, 18F-Labeled Mefway, in Rodents and Imaging by PET in a Nonhuman Primate J. Nucl. Med., October 1, 2006; 47(10): 1697 - 1706. [Abstract] [Full Text] [PDF]