A new model for separation between brain dopamine and serotonin transporters in 123I-?-CIT SPECT measurements: normal values and sex and age dependence

Abstract

123I-beta-CIT is a radioactive ligand for single-photon emission computed tomography (SPECT) imaging of the pre-synaptic (transporter) re-uptake sites for dopamine (DAT) and serotonin (5HTT), and it is widely used to visualize monoamine turnover. Since 123I-beta-CIT uptake occurs at 5HTT and DAT sites in conjunction with the presence of freely soluble 123I-beta-CIT in brain tissue, adequate separation of these three components is necessary. However, only partial separation is possible with current methods. Two main strategies have previously been used for 123I-beta-CIT component separation, based on the following considerations: (1) the faster uptake rate for 5HTT compared with DAT enables temporal separation by performing 5HTT imaging at 1-2 h and DAT imaging at 20-24 h; (2) blocking the 5HTT re-uptake with citalopram renders 123I-beta-CIT imaging DAT (non-5HTT) specific. In a new analytical model, we combined these two approaches with methods to isolate the passively dissolved 123I-beta-CIT in brain tissue from the monoamine transporter uptake, and to correct the 5HTT and DAT values for concomitant uptake. The new analytical model was used to study brain 5HTT and DAT in 23 normal subjects, with the aim of clarifying the effect of age and sex. A significant correlation between 5HTT and DAT values was found only in the thalamus, indicating successful component separation. Negative correlations between age and DAT were found for basal ganglia, thalami, brain stem and temporal lobes, but not for the frontal, parietal or occipital regions. No correlation with age was found for 5HTT. We found no sex difference for 5HTT or DAT.

Altered serotonin and dopamine transporter availabilities in brain of depressed patients upon treatment with escitalopram: A [123I]β-CIT SPECT study

“…The specific binding of [ 123 I]β-CIT to SERT declined by 5% per decade in the diencephalon of healthy subjects (Pirker et al, 2000) or by 4.2% per decade in brainstem-diencephalon (van Dyck et al, 2000). However, others reported no correlation of SERT with age (Ryding et al, 2004) or an only 2% decline per decade in healthy women (Kuikka et al, 2001). Thus, our findings of a 4.4% decline in DAT and a 4.2% decline in SERT per decade of aging are within the corresponding ranges of earlier estimates in healthy subjects, suggesting no main effect of MDD on monoamine transporter changes with age.…”

Direct comparison of FP-CIT SPECT and F-DOPA PET in patients with Parkinson’s disease and healthy controls

“…This is in agreement with some studies which also could not detect an effect of gender on FP-CIT uptake or F-DOPA uptake [45,46]. However, other studies have suggested that DAT tracer and F-DOPA uptake values are higher in women than in men [34,[47][48][49].…”

Serotonin and Dopamine Transporter Availabilities Correlate with the Loudness Dependence of Auditory Evoked Potentials in Patients with Obsessive-Compulsive Disorder

“…Besides the lack of selectivity of b-CIT, our approach to investigate DAT and SERT in the same SPECT session approximately 20-24 h after injection of the tracer is a matter of discussion and has been criticized. Ryding et al (2004) presented a new analytical model for the separation of DAT and SERT in b-CIT-SPECT measurements. Based on SPECT recordings at 1, 6, and 22 h after injection of b-CIT and using citalopram in order to block SERT uptake in the course of the experiment, the authors could demonstrate a successful separation of SERT and DAT, which is a clear advantage of this method compared with our approach.…”

“…However, given functional interactions between monoaminergic systems (Moukhles et al, 1997;Kugaya et al, 2003), this would not be contradictory to the notion of LD as a clinical serotonergic marker (Hegerl et al, 2001;Croft et al, 2001). New models for b-CIT measurements with an improved separation of b-CIT binding to SERT and DAT as proposed by Ryding et al (2004), as well as the use of highly selective radioligands for SERT, such as ADAM for SPECT or DASB for PET (Oya et al, 2000;Kauppinen et al, 2003;Wilson et al, 2002;Frankle et al, 2004), might help to advance in vivo studies and to investigate the different aspects of central monoaminergic function more accurately.…”