1. ¹Department of Radiology, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands
2. ²Graduate School Neurosciences Amsterdam, The Netherlands
3. ³Department of Nuclear Medicine, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands
4. ⁴Amsterdam Institute for Addiction Research and Department of Psychiatry, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands

Correspondence: Dr MML de Win, Department of Radiology, G1-229, Academic Medical Center, University of Amsterdam, Meibergdreef 9, 1105 AZ Amsterdam, The Netherlands. Tel: +31 20 5662690; Fax: +31 20 5669119; E-mail: m.m.dewin@amc.uva.nl

Received 18 June 2004; Revised 15 October 2004; Accepted 6 December 2004; Published online 16 March 2005.

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