title: Characterization of 4-[18F]-ADAM as an imaging agent for SERT in non-human primate brain using PET: a dynamic study.
abstract: BACKGROUND
  Serotonin transporter (SERT) has been associated with many psychiatric diseases. This study investigated the biodistribution of a serotonin transporter imaging agent, N,N-dimethyl-2-(2-amino-4-(18)F-fluorophenylthio)benzylamine (4-[(18)F]-ADAM), in nonhuman primate brain using positron emission tomography (PET).
  
  
  METHODS
  Six and four Macaca cyclopis monkeys were used to determine the transit time (i.e., time necessary to reach biodistribution equilibrium) and the reproducibility of 4-[(18)F]-ADAM biodistribution in the brain, respectively. The sensitivity and specificity of 4-[(18)F]-ADAM binding to SERT were evaluated in one monkey challenged with different doses of fluoxetine and one monkey treated with 3,4-methylendioxymethamphetamine (MDMA). Dynamic PET imaging was performed for 3 h after 4-[(18)F]-ADAM intravenous bolus injection. The specific uptake ratios (SURs) in the midbrain (MB), thalamus (TH), striatum (ST) and frontal cortex (FC) were calculated.
  
  
  RESULTS
  The distribution of 4-[(18)F]-ADAM reached equilibrium 120-150 min after injection. The mean SURs were 2.49 ± 0.13 in MB, 1.59 ± 0.17 in TH, 1.35 ± 0.06 in ST and 0.34 ± 0.03 in FC, and the minimum variability was shown 120-150 min after 4-[(18)F]-ADAM injection. Using SURs and intraclass coefficient of correlation, the test/retest variability was under 8% and above 0.8, respectively, in SERT-rich areas. Challenge with fluoxetin (0.75-2 mg) dose-dependently inhibited the SURs in various brain regions. 4-[(18)F]-ADAM binding was markedly reduced in the brain of an MDMA-treated monkey compared to that in brains of normal controls.
  
  
  CONCLUSIONS
  4-[(18)F]-ADAM appears to be a highly selective radioligand for imaging SERT in monkey brain.
authors.affiliation: Graduate Institute of Life Sciences, National Defense Medical Center, 114 Taipei, Taiwan.
authors.forename: Yu-An
authors.initials: YA
authors.lastname: Chen
authors.forename: Wen-Sheng
authors.initials: WS
authors.lastname: Huang
authors.forename: Yaoh-Shiang
authors.initials: YS
authors.lastname: Lin
authors.forename: Cheng-Yi
authors.initials: CY
authors.lastname: Cheng
authors.forename: Ren-Shyan
authors.initials: RS
authors.lastname: Liu
authors.forename: Shyh-Jen
authors.initials: SJ
authors.lastname: Wang
authors.forename: I-Hsun
authors.initials: IH
authors.lastname: Li
authors.forename: San-Yuan
authors.initials: SY
authors.lastname: Huang
authors.forename: Chyng-Yann
authors.initials: CY
authors.lastname: Shiue
authors.forename: Cheng-Yu
authors.initials: CY
authors.lastname: Chen
authors.forename: Kuo-Hsing
authors.initials: KH
authors.lastname: Ma
mesh_terms: D000818:Animals; D001596:Benzylamines / Q000493:pharmacokinetics*; D001921:Brain / Q000000981:diagnostic imaging* / Q000378:metabolism; D005260:Female; D005462:Fluorine Radioisotopes / Q000493:pharmacokinetics*; D005473:Fluoxetine / Q000494:pharmacology; D008251:Macaca; D008297:Male; D018817:N-Methyl-3,4-methylenedioxyamphetamine / Q000494:pharmacology; D049268:Positron-Emission Tomography / Q000379:methods*; D015203:Reproducibility of Results; D012680:Sensitivity and Specificity; D018490:Serotonin Agents / Q000494:pharmacology; D050486:Serotonin Plasma Membrane Transport Proteins / Q000378:metabolism*; D017367:Selective Serotonin Reuptake Inhibitors / Q000494:pharmacology; D014018:Tissue Distribution
chemical_list: D001596:Benzylamines; D005462:Fluorine Radioisotopes; D005473:Fluoxetine; D018817:N-Methyl-3,4-methylenedioxyamphetamine; D018490:Serotonin Agents; D050486:Serotonin Plasma Membrane Transport Proteins; D017367:Selective Serotonin Reuptake Inhibitors; C475911:N,N-dimethyl-2-(2-amino-4-fluorophenylthio)benzylamine