Quantification of striatal dopamine transporters with 123I-FP-CIT SPECT is influenced by the selective serotonin reuptake inhibitor paroxetine: a double-blind, placebo-controlled, crossover study in healthy control subjects.
Dopamine transporter (DAT) imaging with (123)I-FP-CIT ((123)I-N-omega-fluoropropyl-2beta-carbomethoxy-3beta-(4-iodophenyl)nortropane) SPECT is frequently used to detect loss of nigrostriatal cells in parkinsonism. Recent (123)I-beta-CIT ((123)I-2beta-carbomethoxy-3beta-(4-iodophenyl)tropane) studies have shown a significant increase in striatal-to-nonspecific beta-CIT binding ratios after treatment with selective serotonin reuptake inhibitors (SSRIs). Due to similarities between (123)I-beta-CIT and (123)I-FP-CIT (both are derived from cocaine and show relatively high affinity for the DAT and the serotonin transporter [SERT]), we hypothesized that quantification of striatal (123)I-FP-CIT binding may be influenced by SSRIs. Moreover, we hypothesized that (123)I-FP-CIT in humans binds not only to DATs but also to central and peripheral SERTs.


METHODS
To study the influence of the SSRI paroxetine on (123)I-FP-CIT binding to DATs in the striatum, we conducted a double-blind, placebo-controlled, crossover study with paroxetine in 8 healthy young male control subjects. In addition, we studied whether paroxetine was able to block (123)I-FP-CIT binding in SERT-rich brain areas and in lung tissue, as lung tissue contains a considerable amount of SERTs. Participants were pretreated for 2 d with paroxetine (20 mg/d) or placebo at 2 sessions (crossover design), and brain SPECT was performed 1 and 3 h after (123)I-FP-CIT injection, whereas lung uptake was measured 2 h after injection.


RESULTS
Compared with placebo pretreatment, we found after paroxetine pretreatment a statistically significant increase (approximately 10%) in specific striatal-to-nonspecific (123)I-FP-CIT binding ratios at 3 h after injection, a time point at which striatal (123)I-FP-CIT binding ratios are stable. In addition, after paroxetine treatment, statistically significantly lower binding ratios were found in SERT-rich brain areas (e.g., at 1 h after injection, midbrain-to-cerebellar ratios were approximately 90% lower) as well as significantly lower uptake in lung tissue was found (approximately 40% lower after paroxetine).


CONCLUSIONS
In this study we show that the quantification of striatal (123)I-FP-CIT binding to DAT is significantly increased by the SSRI paroxetine in humans. To our knowledge, this is the first study which shows that (123)I-FP-CIT binds in vivo in humans not only to DATs but also to central SERTs and SERTs in lung tissue.
Booij
Jan
J
Department of Nuclear Medicine, University of Amsterdam, Academic Medical Center, Amsterdam, The Netherlands. J.Booij@amc.uva.nl
de Jong
Jan
J
de Bruin
Kora
K
Knol
Remco
R
de Win
Maartje M L
MM
van Eck-Smit
Berthe L F
BL
D000328:Adult; D003342:Corpus Striatum / Q000737:chemistry*; D018592:Cross-Over Studies; D050483:Dopamine Plasma Membrane Transport Proteins / Q000032:analysis*; D004311:Double-Blind Method; D006801:Humans; D007457:Iodine Radioisotopes; D008297:Male; D017374:Paroxetine / Q000097:blood / Q000494:pharmacology*; D050486:Serotonin Plasma Membrane Transport Proteins / Q000378:metabolism; D017367:Selective Serotonin Reuptake Inhibitors / Q000494:pharmacology*; D015899:Tomography, Emission-Computed, Single-Photon; D014326:Tropanes
D050483:Dopamine Plasma Membrane Transport Proteins; D007457:Iodine Radioisotopes; D017374:Paroxetine; D050486:Serotonin Plasma Membrane Transport Proteins; D017367:Selective Serotonin Reuptake Inhibitors; D014326:Tropanes; C087552:2-carbomethoxy-8-(3-fluoropropyl)-3-(4-iodophenyl)tropane