Validation of [123I]β-CIT SPECT to 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 123iodine-labeled 2β-carbomethoxy-3β(4-iodophenyl)tropane ([123I]β-CIT) and single photon emission computed tomography (SPECT). Validation of this technique is important because [123I]β-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 [ 123I]β-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 [123I]β-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 [123I]β-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 [123I] β-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 [ 123I]β-CIT SPECT may be used to measure SERTs in SERT-low cortical areas, these measurements must be interpreted with caution. © 2005 Nature Publishing Group All rights reserved.