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.

UNLABELLED: 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).

CONCLUSION: 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.