title: SPECT imaging with the serotonin transporter radiotracer [123I]p ZIENT in nonhuman primate brain.
abstract: BACKGROUND
  Serotonin dysfunction has been linked to a variety of psychiatric diseases; however, an adequate SPECT radioligand to probe the serotonin transporter system has not been successfully developed. The purpose of this study was to characterize and determine the in vivo selectivity of iodine-123-labeled 2beta-carbomethoxy-3beta-(4'-((Z)-2-iodoethenyl)phenyl)nortropane, [(123)I]p ZIENT, in nonhuman primate brain.
  
  
  METHODS
  Two ovariohysterectomized female baboons participated in nine studies (one bolus and eight bolus to constant infusion at a ratio of 9.0 h) to evaluate [(123)I]p ZIENT. To evaluate the selectivity of [(123)I]p ZIENT, the serotonin transporter blockers fenfluramine (1.5, 2.5 mg/kg) and citalopram (5 mg/kg), the dopamine transporter blocker methylphenidate (0.5 mg/kg) and the norepinephrine transporter blocker nisoxetine (1 mg/kg) were given at 8 h post-radiotracer injection.
  
  
  RESULTS
  In the bolus to constant infusion studies, equilibrium was established by 4-8 h. [(123)I]p ZIENT was 93% and 90% protein bound in the two baboons and there was no detection of lipophilic radiolabeled metabolites entering the brain. In the high-density serotonin transporter regions (diencephalon and brainstem), fenfluramine and citalopram resulted in 35-71% and 129-151% displacement, respectively, whereas methylphenidate and nisoxetine did not produce significant changes (<10%).
  
  
  CONCLUSIONS
  These findings suggest that [(123)I]p ZIENT is a favorable compound for in vivo SPECT imaging of serotonin transporters with negligible binding to norepinephrine and dopamine transporters.
authors.affiliation: Yale University School of Medicine, VA Connecticut HCS (116A6), West Haven, CT 06516, USA. kelly.cosgrove@yale.edu
authors.forename: Kelly P
authors.initials: KP
authors.lastname: Cosgrove
authors.forename: Julie K
authors.initials: JK
authors.lastname: Staley
authors.forename: Ronald M
authors.initials: RM
authors.lastname: Baldwin
authors.forename: Frederic
authors.initials: F
authors.lastname: Bois
authors.forename: Christophe
authors.initials: C
authors.lastname: Plisson
authors.forename: Mohammed S
authors.initials: MS
authors.lastname: Al-Tikriti
authors.forename: John P
authors.initials: JP
authors.lastname: Seibyl
authors.forename: Mark M
authors.initials: MM
authors.lastname: Goodman
authors.forename: Gilles D
authors.initials: GD
authors.lastname: Tamagnan
mesh_terms: D000818:Animals; D001921:Brain / Q000000981:diagnostic imaging / Q000378:metabolism; D005260:Female; D007457:Iodine Radioisotopes; D009662:Nortropanes / Q000378:metabolism* / Q000493:pharmacokinetics; D010215:Papio; D050486:Serotonin Plasma Membrane Transport Proteins / Q000378:metabolism*; D013379:Substrate Specificity; D015899:Tomography, Emission-Computed, Single-Photon / Q000379:methods*
chemical_list: C472792:2-carbomethoxy-3-(4'-(2-iodoethenyl)phenyl)nortropane; D007457:Iodine Radioisotopes; D009662:Nortropanes; D050486:Serotonin Plasma Membrane Transport Proteins