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

  title={Effective MicroPET imaging of brain 5‐HT1A receptors in rats with [18F]MeFWAY by suppression of radioligand defluorination},
  author={Jae Yong Choi and Chul Hoon Kim and Tae Joo Jeon and Byoung Soo Kim and Chi Hoon Yi and Kwang Sun Woo and Young Beom Seo and Sang Jin Han and KyeongMin Kim and Dae Ik Yi and Minkyung Lee and Dong Goo Kim and Jung Young Kim and Kyochul Lee and Tae-Hyun Choi and Gwang Il An and Young Hoon Ryu},
  • J. ChoiC. Kim Y. Ryu
  • Published 1 December 2012
  • Biology, Medicine, Chemistry
  • Synapse
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… 

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

[18F]Mefway exhibits favorable characteristics compared to [18F]:FCWAY in rodents, and may be a promising radioligand for use in human subjects.

First-in-Human Evaluation of 18F-Mefway, a PET Radioligand Specific to Serotonin-1A Receptors

The simple radiosynthesis, high specific binding profile, and absence of PET signal in bone make 18F-mefway an attractive radiotracer for PET experiments examining the 5-HT1A receptor in neuropsychiatric disorders and drug intervention in humans.

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.

Dopaminergic neuron destruction reduces hippocampal serotonin 1A receptor uptake of trans-[(18)F]Mefway.

  • Minkyung LeeY. Ryu J. Choi
  • Biology, Psychology
    Applied radiation and isotopes : including data, instrumentation and methods for use in agriculture, industry and medicine
  • 2014

Optimization of the radiosynthesis of [(18) F]MEFWAY for imaging brain serotonin 1A receptors by using the GE TracerLab FXFN-Pro module.

  • J. ChoiC. Kim T. Jeon
  • Chemistry
    Journal of labelled compounds & radiopharmaceuticals
  • 2013
The aim of this study was to develop a highly reliable radiofluorination method for the preparation of N-{2-[4-(2-methoxyphenyl)piperazinyl]ethyl}-N-(2-pyridyl)-N-(4-(18)

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.

Radiofluorinated N-Octanoyl Dopamine ([18F]F-NOD) as a Tool To Study Tissue Distribution and Elimination of NOD in Vitro and in Vivo.

In vitro, low cell association was found for [18F]5, indicating no active transport mechanism into cells, and data suggest that also NOD might be cleared fast, further pharmacokinetic evaluation is warranted.

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

Acute physical stress induces the alteration of the serotonin 1A receptor density in the hippocampus

The data illustrates that an acute physical stress induces the change in the serotonergic system that correlates with the behavioral despair.

Relationship between dopamine deficit and the expression of depressive behavior resulted from alteration of serotonin system

It is demonstrated that the destruction of dopaminergic system causes the reduction of the serotonergic system resulting in the expression of depressive behavior.



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.

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.

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).

Brain Uptake of the Acid Metabolites of F-18—Labeled WAY 100635 Analogs

  • R. CarsonYanjun Wu W. Eckelman
  • Biology, Chemistry
    Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism
  • 2003
Simulations based on [18f]FCWAY human data showed that [18F]FC uptake produces significant biases in V estimates in regions with low specific binding, which can be used to correct the tissue [18FsFCWAYWAY time-activity data for brain uptake of [18 f]FC using the measured [18 F]FC input function.

PET evaluation of [(18)F]FCWAY, an analog of the 5-HT(1A) receptor antagonist, WAY-100635.

Quantification of serotonin 5‐HT1A receptors in monkey brain with [11C](R)‐(−)‐RWAY

Different tracer kinetic models in nonhuman primates to quantify 5‐HT1A receptors with [11C](R)‐(−)‐RWAY and to test for the possible action of P‐glycoprotein (P‐gp), one of the known efflux pumps at the blood–brain barrier were evaluated.

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.

The high ratios in specific brain regions such as the hippocampus suggest that 18F-mefway has potential as a PET agent for 5HT1A receptors, and synthesized N-{2-[4-methoxyphenyl)piperazinyl]ethyl}-N-(2-pyridyl)-N-(4-18F-fluoromethylcyclohexane)carboxamide (18F -FCWAY).