title: Re-evaluation of in vivo selectivity of [(11)C]SA4503 to σ(1) receptors in the brain: contributions of emopamil binding protein.
abstract: BACKGROUND
  Carbon-11-labeled 1-[2-(3,4-dimethoxyphenyl)ethyl]-4-(3-phenylpropyl)piperazine ([(11)C]SA4503) was shown to be a promising PET ligand for mapping σ(1) receptors, and was applied to human subjects. However, an in vitro study indicated that SA4503 also binds to the emopamil binding protein (EBP), vertebral Δ8-Δ7 sterol isomerase. To our knowledge, no information is available about the possibility of [(11)C]SA4503 binding to EBP in the brain in vivo.
  
  
  METHODS
  To confirm the selectivity of [(11)C]SA4503, we carried out an in vivo blocking experiment using high-affinity EBP and σ(1) selective blocker.
  
  
  RESULTS
  The brain uptake of [(11)C]SA4503 was dose-dependently decreased by SA4503 and the high-affinity σ(1) blockers haloperidol, ifenprodil, and trifluperidol. On the other hand, the effects of the high-affinity EBP blockers tamoxifen and trifluoperazine were negligible.
  
  
  CONCLUSIONS
  Our results confirmed the σ(1)-selective binding of [(11)C]SA4503 in the brain.
authors.affiliation: Positron Medical Center, Tokyo Metropolitan Institute of Gerontology, 1-1, Naka, Itabashi, Tokyo 173-0022, Japan. toyohara@pet.tmig.or.jp
authors.forename: Jun
authors.initials: J
authors.lastname: Toyohara
authors.forename: Muneyuki
authors.initials: M
authors.lastname: Sakata
authors.forename: Kiichi
authors.initials: K
authors.lastname: Ishiwata
mesh_terms: D000818:Animals; D001692:Biological Transport / Q000187:drug effects; D001921:Brain / Q000187:drug effects / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D006168:Guinea Pigs; D006801:Humans; D051379:Mice; D010879:Piperazines / Q000378:metabolism*; D051381:Rats; D017480:Receptors, sigma / Q000037:antagonists & inhibitors / Q000378:metabolism*; D013251:Steroid Isomerases / Q000378:metabolism*; D013379:Substrate Specificity
chemical_list: D010879:Piperazines; D017480:Receptors, sigma; C101789:SA 4503; D013251:Steroid Isomerases; C090445:EBP protein, human