title: In vivo kinetics of [F-18]MEFWAY: a comparison with [C-11]WAY100635 and [F-18]MPPF in the nonhuman primate.
abstract: [F-18]Mefway was developed to provide an F-18 labeled positron emission tomography (PET) neuroligand with high affinity for the serotonin 5-HT(1A) receptor to improve the in vivo assessment of the 5-HT(1A) system. The goal of this work was to compare the in vivo kinetics of [F-18]mefway, [F-18]MPPF, and [C-11]WAY100635 in the rhesus monkey.
  
  
  METHODS
  Each of four monkeys were given bolus injections of [F-18]mefway, [C-11]WAY100635, and [F-18]MPPF and scans were acquired with a microPET P4 scanner. Arterial blood was sampled to assay parent compound throughout the time course of the PET experiment. Time activity curves were extracted in the high 5-HT(1A) binding areas of the anterior cingulate cortex (ACG), mesial temporal cortex, raphe nuclei, and insula cortex. Time activity curves were also extracted in the cerebellum, which was used as a reference region. The in vivo kinetics of the radiotracers were compared based on the nondisplaceable distribution volume (V(ND) ) and binding potential (BP(ND) ).
  
  
  RESULTS
  At 30 min, the fraction of radioactivity in the plasma due to parent compound was 19%, 28%, and 29% and cleared from the arterial plasma at rates of 0.0031, 0.0078, and 0.0069 (min⁻¹) ([F-18]mefway, [F-18]MPPF, [C-11]WAY100635). The BP(ND) in the brain regions were mesial temporal cortex: 7.4 ± 0.6, 3.1 ± 0.4, 7.0 ± 1.2, ACG: 7.2 ± 1.2, 2.1 ± 0.2, 7.9 ± 1.2; raphe nuclei: 3.7 ± 0.6, 1.3 ± 0.3, 3.3 ± 0.7; and insula cortex: 4.2 ± 0.6, 1.2 ± 0.1, 4.7 ± 1.0 for [F-18]mefway, [F-18]MPPF, and [C-11]WAY100635 respectively.
  
  
  CONCLUSIONS
  In the rhesus monkey, [F-18]mefway has similar in vivo kinetics to [C-11]WAY100635 and yields greater than 2-fold higher BP(ND) than [F-18]MPPF. These properties make [F-18]mefway a promising radiotracer for 5-HT(1A) assay, providing higher counting statistics and a greater dynamic range in BP(ND).
authors.affiliation: Department of Medical Physics, Harlow Primate Center, Waisman Laboratory for Brain Imaging and Behavior, University of Wisconsin-Madison, Madison, Wisconsin 53593, USA.
authors.forename: D W
authors.initials: DW
authors.lastname: Wooten
authors.forename: J D
authors.initials: JD
authors.lastname: Moraino
authors.forename: A T
authors.initials: AT
authors.lastname: Hillmer
authors.forename: J W
authors.initials: JW
authors.lastname: Engle
authors.forename: O J
authors.initials: OJ
authors.lastname: Dejesus
authors.forename: D
authors.initials: D
authors.lastname: Murali
authors.forename: T E
authors.initials: TE
authors.lastname: Barnhart
authors.forename: R J
authors.initials: RJ
authors.lastname: Nickles
authors.forename: R J
authors.initials: RJ
authors.lastname: Davidson
authors.forename: M L
authors.initials: ML
authors.lastname: Schneider
authors.forename: J
authors.initials: J
authors.lastname: Mukherjee
authors.forename: B T
authors.initials: BT
authors.lastname: Christian
mesh_terms: D000818:Animals; D001921:Brain / Q000000981:diagnostic imaging*; D002250:Carbon Radioisotopes / Q000493:pharmacokinetics; D005462:Fluorine Radioisotopes / Q000493:pharmacokinetics; D008253:Macaca mulatta; D010879:Piperazines / Q000493:pharmacokinetics*; D049268:Positron-Emission Tomography / Q000379:methods; D011725:Pyridines / Q000493:pharmacokinetics*; D019275:Radiopharmaceuticals / Q000493:pharmacokinetics*
chemical_list: D002250:Carbon Radioisotopes; D005462:Fluorine Radioisotopes; D010879:Piperazines; D011725:Pyridines; D019275:Radiopharmaceuticals; C515664:mefway; C090413:N-(2-(4-(2-methoxyphenyl)-1-piperazinyl)ethyl)-N-(2-pyridinyl)cyclohexanecarboxamide