title: An in vivo comparison of cis- and trans-[18F]mefway in the nonhuman primate.
abstract: BACKGROUND
  [(18)F]Mefway is a serotonin 5-HT(1A) PET radiotracer with high specificity and favorable in vivo imaging properties. The chemical structure of [(18)F]mefway permits (18)F labeling in either the cis or trans positions at the 4-cyclohexyl site. We have previously reported on the in vivo kinetics of trans-[(18)F]mefway in the nonhuman primate. In this work, we compare the in vivo binding of cis-[(18)F]mefway and trans-[(18)F]mefway to evaluate the properties of cis-[(18)F]mefway for 5-HT(1A) PET imaging.
  
  
  METHODS
  The cis- and trans-[(18)F]mefway tracers were synthesized via nucleophilic substitution with their respective tosyl precursors. Two monkeys (one male, one female) were given bolus injections of both cis- and trans-labeled [(18)F]mefway in separate experiments. Dynamic scans were acquired for 90 min with a microPET P4 scanner. Time-activity curves were extracted in the areas of the mesial temporal cortex (MTC), anterior cingulate gyrus (aCG), insular cortex (IC), raphe nuclei (RN) and cerebellum (CB). The in vivo behavior of the radiotracers was compared based upon the nondisplaceable binding potential (BP(ND)) using the CB as a reference region.
  
  
  RESULTS
  Averaged over the two subjects, BP(ND) values were as follows: MTC: 7.7, 0.58; aCG: 4.95, 0.32; IC: 3.27, 0.2; and RN: 3.05, 0.13, for trans-[(18)F]mefway and cis-[(18)F]mefway, respectively.
  
  
  CONCLUSIONS
  The cis-labeled [(18)F]mefway tracer has low specific binding throughout the 5-HT(1A) regions of the brain compared to trans-[(18)F]mefway, suggesting that the target-to-background binding of cis-[(18)F]mefway may limit its use for in vivo assessment of 5-HT(1A) binding.
authors: Department of Medical Physics, Waisman Laboratory for Brain Imaging and Behavior, University of Wisconsin-Madison, Madison, WI 53705, USA. dwooten@wisc.edu
authors: Dustin
authors: D
authors: Wooten
authors: Ansel
authors: A
authors: Hillmer
authors: Dhanabalan
authors: D
authors: Murali
authors: Todd
authors: T
authors: Barnhart
authors: Mary L
authors: ML
authors: Schneider
authors: Jogeshwar
authors: J
authors: Mukherjee
authors: Bradley T
authors: BT
authors: Christian
mesh_terms: D000818:Animals; D005260:Female; D005462:Fluorine Radioisotopes; D007700:Kinetics; D008253:Macaca mulatta / Q000378:metabolism*; D008297:Male; D010879:Piperazines / Q000032:analysis / Q000737:chemistry* / Q000493:pharmacokinetics; D049268:Positron-Emission Tomography; D011725:Pyridines / Q000032:analysis / Q000737:chemistry* / Q000493:pharmacokinetics; D011849:Radioactive Tracers; D044282:Receptor, Serotonin, 5-HT1A / Q000378:metabolism; D013237:Stereoisomerism
chemical_list: D005462:Fluorine Radioisotopes; D010879:Piperazines; D011725:Pyridines; D011849:Radioactive Tracers; C515664:mefway; D044282:Receptor, Serotonin, 5-HT1A