Translational possibility of [18F]Mefway to image serotonin 1A receptors in humans: Comparison with [18F]FCWAY in rodents

  title={Translational possibility of [18F]Mefway to image serotonin 1A receptors in humans: Comparison with [18F]FCWAY in rodents},
  author={Jae Yong Choi and Byoung Soo Kim and Chul Hoon Kim and Dong Goo Kim and Sang Jin Han and Kyochul Lee and Kyeong‐Min Kim and Gwang Il An and Tae-Hyun Choi and Sun Dong Yoo and Young Hoon Ryu},
  • J. ChoiByoung Soo Kim Y. Ryu
  • Published 1 December 2014
  • Biology, Chemistry
  • Synapse
Purpose: To compare the cerebral uptake and binding potential of [18F]FCWAY and [18F]Mefway in the rodent to assess their potential for imaging serotonin 1A (5‐HT1A) receptors. Materials and Methods: In vitro liver microsomal studies were performed to evaluate the degree of defluorination. Dynamic positron emission tomography (PET) studies were then conducted for 2 h with or without an anti‐defluorination agent. The regions of interest were the hippocampus and frontal cortex (5‐HT1A target… 

18F-Mefway PET Imaging of Serotonin 1A Receptors in Humans: A Comparison with 18F-FCWAY

18F-Mefway may be a good candidate PET radioligand for 5-HT1A receptor imaging in human and the resistance to in vivo defluorination of 18F- Mefway obviates the need for the use of a defLuorination inhibitor.

P-Glycoprotein, not BCRP, Limits the Brain Uptake of [18F]Mefway in Rodent Brain

Mefway is modulated by P-gp, and not by Bcrp in rodents, as shown in Figure 18F.

Optimal timing of [¹⁸F]Mefway PET for imaging the serotonin 1A receptor in healthy male subjects.



Effective MicroPET imaging of brain 5‐HT1A receptors in rats with [18F]MeFWAY by suppression of radioligand defluorination

In the rat brain, [18F]MeFWAY microPET showed skull uptake due to defluorination in vivo, and the authors can effectively overcome this drawback with fluconazole.

In vivo kinetics of [F‐18]MEFWAY: A comparison with [C‐11]WAY100635 and [F‐18]MPPF in the nonhuman primate

In the rhesus monkey, [F‐18]mefway has similar in vivo kinetics to [C‐11]WAY100635 and yields greater than 2‐fold higher BPND than [F •18]MPPF, which makes [F•18] mefway a promising radiotracer for 5‐HT1A assay.

PET imaging of brain 5-HT1A receptors in rat in vivo with 18F-FCWAY and improvement by successful inhibition of radioligand defluorination with miconazole.

  • D. TipreS. Zoghbi V. Pike
  • Biology, Chemistry
    Journal of nuclear medicine : official publication, Society of Nuclear Medicine
  • 2006
PET in miconazole-treated rats can serve as an effective platform for investigating 5-HT1A receptors in rodent models of neuropsychiatric conditions or drug action and confirmed the potential of 18F-FCWAY to act as a radioligand for 5- HT1A receptor receptors in rat brain and also revealed extensive defluorination.

Linearized Reference Tissue Parametric Imaging Methods: Application to [11C]DASB Positron Emission Tomography Studies of the Serotonin Transporter in Human Brain

  • M. IchiseJ. Liow R. Carson
  • Medicine
    Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism
  • 2003
Rapid parametric imaging by MRTM2 should be a useful method for human [11C]DASB positron emission tomography studies as it allowed rapid generation of parametric images with the noise reductions consistent with the simulations.

5‐HT radioligands for human brain imaging with PET and SPECT

The development of PET and SPECT radioligands to image serotonergic targets is of high interest, and successful evaluation in humans is leading to invaluable insight into normal and abnormal brain function, emphasizing the need for continued development of both SPECT and PET radiolIGands for human brain imaging.

Evaluation of [18F]Mefway Biodistribution and Dosimetry Based on Whole-Body PET Imaging of Mice

Whole-body mouse imaging can be used as a preclinical tool to provide initial estimates of the absorbed doses of [18F]Mefway in humans.

[carbonyl-11C]Desmethyl-WAY-100635 (DWAY) is a potent and selective radioligand for central 5-HT1A receptors in vitro and in vivo

Investigation of the ability of DWAY to enter brain in vivo and its possible interaction with 5-HT1A receptors shows that intravenously administered DWAY is well able to penetrate brain in rat and monkey and is a highly effective radioligand for brain 5- HT1A receptor receptors inRat and monkey in vitro and for human brain in vitro.

Disulfiram Inhibits Defluorination of 18F-FCWAY, Reduces Bone Radioactivity, and Enhances Visualization of Radioligand Binding to Serotonin 5-HT1A Receptors in Human Brain

Disulfiram is a safe and well-tolerated drug that may be useful for other radioligands that undergo defluorination via CYP2E1, and changed the shape of the brain time–activity curves in a manner that could occur with inhibition of the efflux transporter P-glycoprotein (P-gp).