Effective MicroPET imaging of brain 5-HT1A receptors in rats with [18F]MeFWAY by suppression of radioligand defluorination
Article first published online: 29 SEP 2012
Copyright © 2012 Wiley Periodicals, Inc.
Volume 66, Issue 12, pages 1015–1023, December 2012
How to Cite
Choi, J. Y., Kim, C. H., Jeon, T. J., Kim, B. S., Yi, C. H., Woo, K. S., Seo, Y. B., Han, S. J., Kim, K. M., Yi, D. I., Lee, M., Kim, D. G., Kim, J. Y., Lee, K. C., Choi, T. H., An, G. and Ryu, Y. H. (2012), Effective MicroPET imaging of brain 5-HT1A receptors in rats with [18F]MeFWAY by suppression of radioligand defluorination. Synapse, 66: 1015–1023. doi: 10.1002/syn.21607
- Issue published online: 13 OCT 2012
- Article first published online: 29 SEP 2012
- Accepted manuscript online: 28 AUG 2012 04:03AM EST
- Manuscript Accepted: 21 AUG 2012
- Manuscript Received: 27 JUN 2012
- Korea Science and Engineering Foundation (KOSEF). Grant Number: 2012026787
- Ministry of Science and Technology (MOST), Republic of Korea, through the National Nuclear Technology Program
- 5-HT1A receptors;
Introduction: [18F]MeFWAY has been developed for imaging the serotonin 1A receptors in the brain. The purpose of this study were to verify the metabolic stability of [18F]MeFWAY, to measure the degree of defluorination of [18F]MeFWAY in vivo, to investigate methods of inhibition of defluorination of [18F]MeFWAY, and to assess the efficacy of [18F]MeFWAY in rat brains in vivo. Methods: MicroPET experiments in rats were conducted to confirm the distribution of radioactivity in the brain. Nondisplaceable binding potential (BPND) in the hippocampus and frontal cortex were also analyzed. Miconazole and fluconazole were tested for the ability to suppress defluorination of [18F]MeFWAY. We conducted a blockade and displacement experiment by treating with WAY-100635. Results: In vitro stability tests showed that MeFWAY was very stable in serum for 6 h, but PET revealed that authentic [18F]MeFWAY underwent significant defluorination in vivo. In vitro inhibition study against decreasing parent activity in liver microsomes, miconazole and fluconazole suppressed metabolic elimination of MeFWAY. However, in the PET study, fluconazole showed more potent inhibitory activity than miconazole. In the suppression of metabolizing enzymes using fluconazole, radioactivity in skull was dramatically decreased by 81% (compared with 69% with miconazole) and it was coupled with an increase in brain uptake. Moreover, BPND in hippocampus was 5.53 and 2.66 in frontal cortex. The blockade and displacement study showed the specificity of [18F]MeFWAY to 5-HT1A receptors. Conclusion: In the rat brain, [18F]MeFWAY microPET showed skull uptake due to defluorination in vivo. We can effectively overcome this drawback with fluconazole. Synapse, 2012. © 2012 Wiley Periodicals, Inc.