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de Win MM, Habraken JB, Reneman L, van den Brink W, den Heeten GJ, Booij J. 
“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”. 
Neuropsychopharmacology. 2005 May;30(5):996-1005.
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.Neuropsychopharmacology (2005) 30, 996-1005, advance online publication, 16 March 2005; doi:10.1038/sj.npp.1300683.
Comments and Responses to this Article
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earth / nc
Apr 17, 2011 1:59
Misc Comments #

Small N (6).

Single crossover design (not citalopram first, then placebo and placebo then citalopram).

Used SPECT (single photon emission computed tomography) to look for whether the chosen ligand, [123I]b-CIT, selectively binds to serotonin transporters.

The authors that 'In conclusion, our results provide evidence that [123I]b-CIT SPECT is a valid technique to study SERTs in vivo in humans in SERT-rich brain areas, as binding ratios significantly decreased by pretreatment with the selective SSRI citalopram', but their data shows incomplete displacement of the ligand studied by citalopram, so it is unclear how well this validates this as a ligand for the purpose of measuring SERT.

Without showing that > 80% (to choose an arbitrary number) of the ligand could be displaced, the authors failed to show that the ligand was actually selectively binding to SERT and thus studies done with it where it is assumed to represent SERT can only be (at maximum) as accurate as the maximum displacement shown. So if this paper shows between %50 and 100% displacement in the mid-brain by citalopram (average of about 75%), differences in SPECT measurement of this ligand for mid-brain SERT would have to far exceed the %25 error before it could be assumed to be SERT related instead of affecting something else that the ligand is binding to.

The point of this study is surely to confirm and validate other work showing that ecstasy users have suffered damage to SERT because they showed lower binding of this ligand in certain brain areas. The levels of variability and error shown with this paper should be used to go back and look at research that has been done using this ligand ([123I]b-CIT) using SPECT.
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