title: Validation of [(123)I]beta-CIT SPECT to assess serotonin transporters in vivo in humans: a double-blind, placebo-controlled, crossover study with the selective serotonin reuptake inhibitor citalopram.
abstract: Disturbances in the serotonin (5-HT) system are associated with various neuropsychiatric disorders. The 5-HT system can be studied in vivo by measuring 5-HT transporter (SERT) densities using (123)iodine-labeled 2beta-carbomethoxy-3beta(4-iodophenyl)tropane ([(123)I]beta-CIT) and single photon emission computed tomography (SPECT). Validation of this technique is important because [(123)I]beta-CIT does not bind selectively to SERTs. Some studies have validated this technique in vivo in the human brain in SERT-rich areas, but the technique has not been validated yet in SERT-low cortical areas. The aim of this study was to further validate [(123)I]beta-CIT SPECT in assessing SERTs in vivo in humans in both SERT-rich and SERT-low areas. A double-blind, placebo-controlled, crossover design was used with the selective 5-HT reuptake inhibitor (SSRI) citalopram. Six male subjects underwent two [(123)I]beta-CIT SPECT sessions: one after pretreatment with citalopram and one after placebo. Scans were acquired 4 h and 22-27 h p.i., and both region-of-interest and voxel-by-voxel analyses were performed. Citalopram reduced [(123)I]beta-CIT binding ratios in SERT-rich midbrain and (hypo)thalamus. Binding ratios were also lower after citalopram in SERT-low cortical areas, but statistical significance was only reached in several cortical areas using voxel-by-voxel analysis. In addition, citalopram increased binding ratios in the DAT-rich striatum and increased absolute uptake in the cerebellum. The results show that [(123)I]beta-CIT SPECT is a valid technique to study SERT binding in vivo in human brain in SERT-rich areas. Although we provide some evidence that [(123)I]beta-CIT SPECT may be used to measure SERTs in SERT-low cortical areas, these measurements must be interpreted with caution.
authors.affiliation: Department of Radiology, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands. m.m.dewin@amc.uva.nl
authors.forename: Maartje M L
authors.initials: MM
authors.lastname: de Win
authors.forename: Jan B A
authors.initials: JB
authors.lastname: Habraken
authors.forename: Liesbeth
authors.initials: L
authors.lastname: Reneman
authors.forename: Wim
authors.initials: W
authors.lastname: van den Brink
authors.forename: Gerard J
authors.initials: GJ
authors.lastname: den Heeten
authors.forename: Jan
authors.initials: J
authors.lastname: Booij
mesh_terms: D000293:Adolescent; D000328:Adult; D001921:Brain / Q000000981:diagnostic imaging*; D001923:Brain Chemistry / Q000187:drug effects; D015283:Citalopram / Q000494:pharmacology*; D003042:Cocaine / Q000031:analogs & derivatives*; D018592:Cross-Over Studies; D004311:Double-Blind Method; D005260:Female; D006801:Humans; D007091:Image Processing, Computer-Assisted; D008297:Male; D008562:Membrane Glycoproteins / Q000378:metabolism*; D026901:Membrane Transport Proteins / Q000378:metabolism*; D009419:Nerve Tissue Proteins / Q000378:metabolism*; D019275:Radiopharmaceuticals; D050486:Serotonin Plasma Membrane Transport Proteins; D017367:Selective Serotonin Reuptake Inhibitors / Q000494:pharmacology*; D015899:Tomography, Emission-Computed, Single-Photon
chemical_list: D015283:Citalopram; D003042:Cocaine; D008562:Membrane Glycoproteins; D026901:Membrane Transport Proteins; D009419:Nerve Tissue Proteins; D019275:Radiopharmaceuticals; D050486:Serotonin Plasma Membrane Transport Proteins; D017367:Selective Serotonin Reuptake Inhibitors; C493230:SLC6A4 protein, human; C069723:2beta-carbomethoxy-3beta-(4-iodophenyl)tropane