title: 18F-Mefway PET imaging of serotonin 1A receptors in humans: a comparison with 18F-FCWAY.
abstract: BACKGROUND
  The purpose of this research is to evaluate the prospects for the use of 4-(trans-18F-fluoranylmethyl)-N-[2-[4-(2-methoxyphenyl)piperazin-1-yl]ethyl]-N-pyridin-2-ylcyclohexane-1-carboxamide (18F-Mefway) in comparison to 18F-trans-4-fluoro-N-2-[4-(2-methoxyphenyl)piperazin-1-yl]ethyl]-N-(2-pyridyl)cyclohexanecarboxamide (18F-FCWAY) for the quantification of 5-HT1A receptors in human subjects.
  
  
  METHODS
  Five healthy male controls were included for two positron emission tomography (PET) studies: 18F-FCWAY PET after the pretreatment with 500 mg of disulfiram and two months later, 18F-Mefway PET without disulfiram. Regional time-activity curves (TACs) were extracted from nine cortical and subcortical regions in dynamic PET images. Using cerebellar cortex without vermis as reference tissue, in vivo kinetics for both radioligands were compared based on the distribution volume ratio (DVR) calculated by non-invasive Logan graphical analysis and area under the curve ratio of the TACs (AUC ratio).
  
  
  RESULTS
  Although the pattern of regional uptakes in the 18F-Mefway PET was similar to that of the 18F-FCWAY PET (highest in the hippocampus and lowest in the cerebellar cortex), the amount of regional uptake in 18F-Mefway PET was almost half of that in 18F-FCWAY PET. The skull uptake in 18F-Mefway PET was only 25% of that in 18F-FCWAY PET with disulfiram pretreatment. The regional DVR values and AUC ratio values for 18F-Mefway were 17-40% lower than those of 18F-FCWAY. In contrast to a small overestimation of DVR values by AUC ratio values (< 10%) in 18F-FCWAY PET, the overestimation bias of AUC ratio values was much higher (up to 21%) in 18F-Mefway PET.
  
  
  CONCLUSIONS
  As 18F-Mefway showed lower DVR values and greater overestimation bias of AUC ratio values, 18F-Mefway may appear less favorable than 18F-FCWAY. However, in contrast to 18F-FCWAY, the resistance to in vivo defluorination of 18F-Mefway obviates the need for the use of a defluorination inhibitor. Thus, 18F-Mefway may be a good candidate PET radioligand for 5-HT1A receptor imaging in human.
authors.affiliation: Department of Nuclear Medicine, Gangnam Severance Hospital, Yonsei University College of Medicine, Seoul, Korea.
authors.forename: Jae Yong
authors.initials: JY
authors.lastname: Choi
authors.affiliation: Department of Neurology, Gangnam Severance Hospital, Yonsei University College of Medicine, Seoul, Korea.
authors.forename: Chul Hyoung
authors.initials: CH
authors.lastname: Lyoo
authors.affiliation: Molecular Imaging Research Center, Korea Institute of Radiological and Medical Sciences, Seoul, Korea.
authors.forename: Jin Su
authors.initials: JS
authors.lastname: Kim
authors.affiliation: Molecular Imaging Research Center, Korea Institute of Radiological and Medical Sciences, Seoul, Korea.
authors.forename: Kyeong Min
authors.initials: KM
authors.lastname: Kim
authors.affiliation: Department of Chemistry and Biochemistry, Swarthmore College, 500 College Avenue Swarthmore, PA, United States of America.
authors.forename: Jee Hae
authors.initials: JH
authors.lastname: Kang
authors.affiliation: Department of Psychiatry and Institute of Human Behavioral Sciences, Seoul National University College of Medicine, Seoul, Korea.
authors.forename: Soo-Hee
authors.initials: SH
authors.lastname: Choi
authors.affiliation: Department of Psychiatry and Institute of Behavioral Science in Medicine, Yonsei University College of Medicine, Seoul, Korea.
authors.forename: Jae-Jin
authors.initials: JJ
authors.lastname: Kim
authors.affiliation: Department of Nuclear Medicine, Gangnam Severance Hospital, Yonsei University College of Medicine, Seoul, Korea.
authors.forename: Young Hoon
authors.initials: YH
authors.lastname: Ryu
mesh_terms: D000328:Adult; D019540:Area Under Curve; D001921:Brain / Q000000981:diagnostic imaging / Q000378:metabolism; D003510:Cyclohexanes / Q000138:chemical synthesis / Q000737:chemistry*; D005462:Fluorine Radioisotopes / Q000737:chemistry; D006801:Humans; D008297:Male; D010879:Piperazines / Q000138:chemical synthesis / Q000737:chemistry*; D049268:Positron-Emission Tomography / Q000379:methods*; D011725:Pyridines / Q000138:chemical synthesis / Q000737:chemistry*; D012372:ROC Curve; D019275:Radiopharmaceuticals / Q000138:chemical synthesis / Q000737:chemistry*; D044282:Receptor, Serotonin, 5-HT1A / Q000378:metabolism; D012886:Skull / Q000000981:diagnostic imaging / Q000378:metabolism; D014057:Tomography, X-Ray Computed
chemical_list: D003510:Cyclohexanes; D005462:Fluorine Radioisotopes; C493883:N-(2-(4-(2-methoxyphenyl)piperazino))-N-(2-pyridinyl) trans-4-fluorocyclohexanecarboxamide; D010879:Piperazines; D011725:Pyridines; D019275:Radiopharmaceuticals; C515664:mefway; D044282:Receptor, Serotonin, 5-HT1A
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