TY - JOUR T1 - Quantification of Striatal Dopamine Transporters with <sup>123</sup>I-FP-CIT SPECT Is Influenced by the Selective Serotonin Reuptake Inhibitor Paroxetine: A Double-Blind, Placebo-Controlled, Crossover Study in Healthy Control Subjects JF - Journal of Nuclear Medicine JO - J Nucl Med SP - 359 LP - 366 VL - 48 IS - 3 AU - Jan Booij AU - Jan de Jong AU - Kora de Bruin AU - Remco Knol AU - Maartje M.L. de Win AU - Berthe L.F. van Eck-Smit Y1 - 2007/03/01 UR - http://jnm.snmjournals.org/content/48/3/359.abstract N2 - Dopamine transporter (DAT) imaging with 123I-FP-CIT (123I-N-ω-fluoropropyl-2β-carbomethoxy-3β-(4-iodophenyl)nortropane) SPECT is frequently used to detect loss of nigrostriatal cells in parkinsonism. Recent 123I-β-CIT (123I-2β-carbomethoxy-3β-(4-iodophenyl)tropane) studies have shown a significant increase in striatal-to-nonspecific β-CIT binding ratios after treatment with selective serotonin reuptake inhibitors (SSRIs). Due to similarities between 123I-β-CIT and 123I-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 123I-FP-CIT binding may be influenced by SSRIs. Moreover, we hypothesized that 123I-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 123I-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 123I-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 123I-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 123I-FP-CIT binding ratios at 3 h after injection, a time point at which striatal 123I-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 123I-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 123I-FP-CIT binds in vivo in humans not only to DATs but also to central SERTs and SERTs in lung tissue. ER -