title: Translational possibility of [18F]Mefway to image serotonin 1A receptors in humans: Comparison with [18F]FCWAY in rodents.
abstract: OBJECTIVE
  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.
  
  
  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-HT1Atarget regions) and the cerebellum (5-HT1Anontarget region). The in vivo kinetics of the radioligands were compared based on the brain uptake values and target-to-nontarget ratio. We also performed a comparison of binding potential (BPND) as a steady-state binding parameter. Finally, binding affinities to 5-HT1Areceptors were assessed in Chinese hamster ovary cells (CHO-K1) cells expressing human recombinant 5-HT1Areceptors.
  
  
  RESULTS
  The radiochemical yield of [18F]Mefway was slightly higher than that of [18F]FCWAY (19 vs. 15%). With regard to metabolic stability against defluorination, both compounds exhibited similar stability in rat liver microsomes, but [18F]Mefway displayed higher stability in the human microsome (defluorination ratio at 30 min: 32 vs. 29 in rat liver microsomes, 31 vs. 64 in human liver microsomes for [18F]Mefway and [18F]FCWAY, respectively). There were no significant differences in brain uptake, the target-to-nontarget ratios, and the BPND(at hippocampus, peak brain uptakes: 6.9 vs. 8.5, target-to-nontarget ratios: 6.9 vs. 8.5, BPND: 5.2 vs. 6.2 for [18F]Mefway and [18F]FCWAY). The binding affinity of [18F]Mefway was considerably higher than that of [18F]FCWAY (IC50: 1.5 nM vs. 2.2 nM).
  
  
  CONCLUSIONS
  [18F]Mefway exhibits favorable characteristics compared to [18F]FCWAY in rodents, and may be a promising radioligand for use in human subjects. Synapse 68:595-603, 2014. © 2014 Wiley Periodicals, Inc.
authors: Department of Nuclear Medicine, Yonsei University College of Medicine, Gangnam Severance Hospital, Seoul, 135-720, Korea.
authors: Jae Yong
authors: JY
authors: Choi
authors: Department of Molecular Imaging, Korea Institute of Radiological and Medical Sciences, Seoul, 139-706, Korea.
authors: Byoung Soo
authors: BS
authors: Kim
authors: Department of Pharmacology, Brain Research Institute, Brain Korea 21 Project for Medical Science, Yonsei University College of Medicine, Seoul, 120-752, Korea.
authors: Chul Hoon
authors: CH
authors: Kim
authors: Department of Pharmacology, Brain Research Institute, Brain Korea 21 Project for Medical Science, Yonsei University College of Medicine, Seoul, 120-752, Korea.
authors: Dong Goo
authors: DG
authors: Kim
authors: Department of Nuclear Medicine, Yonsei University College of Medicine, Gangnam Severance Hospital, Seoul, 135-720, Korea.
authors: Sang Jin
authors: SJ
authors: Han
authors: Department of Molecular Imaging, Korea Institute of Radiological and Medical Sciences, Seoul, 139-706, Korea.
authors: Kyochul
authors: K
authors: Lee
authors: Department of Molecular Imaging, Korea Institute of Radiological and Medical Sciences, Seoul, 139-706, Korea.
authors: Kyeong Min
authors: KM
authors: Kim
authors: Department of Molecular Imaging, Korea Institute of Radiological and Medical Sciences, Seoul, 139-706, Korea.
authors: Gwangil
authors: G
authors: An
authors: Department of Molecular Imaging, Korea Institute of Radiological and Medical Sciences, Seoul, 139-706, Korea.
authors: Tae Hyun
authors: TH
authors: Choi
authors: College of Pharmacy, Sungkyunkwan University, Suwon, Gyeonggi-do, 440-746, Korea.
authors: Sun Dong
authors: SD
authors: Yoo
authors: Department of Nuclear Medicine, Yonsei University College of Medicine, Gangnam Severance Hospital, Seoul, 135-720, Korea.
authors: Young Hoon
authors: YH
authors: Ryu
keywords: [18F]FCWAY; [18F]Mefway; microPET; serotonin 1A receptors