Comparative in vivo study of iodine-123-labeled ?-cit and nor-?-cit binding to serotonin transporters in rat brain

Abstract

Both iodine-123-labeled beta-CIT (2beta-carbomethoxy-3beta-(4-iodophenyl)tropane) and nor-beta-CIT (2beta-carbomethoxy-3beta-(4-iodophenyl)nortropane) have shown to be suitable radioligands for imaging serotonin (5-HT) transporters. [(123)I]nor-beta-CIT has the highest in vitro affinity for 5-HT transporters among beta-CIT analogs reported so far. However, no direct comparison-studies of these two radiotracers as to their in vivo binding to 5-HT transporters have been reported so far. Therefore, it is still unclear which of the two radiotracers is more suitable for single photon emission computed tomography (SPECT) imaging of 5-HT transporters. The purpose of this study was to compare directly in a controlled design the in vivo [(123)I]beta-CIT and [(123)I]nor-beta-CIT binding to 5-HT transporters under the same conditions in rats with the focus on brain kinetic characteristics by means of a two-compartment analysis. We observed that [(123)I]beta-CIT has a higher binding potential and faster kinetics for 5-HT transporters than [(123)I]nor-beta-CIT, suggesting that [(123)I]beta-CIT may be a more suitable radioligand than [(123)I]nor-beta-CIT for imaging 5-HT transporters with SPECT.

Addition of a 5-HT receptor agonist to methylphenidate potentiates the reduction of [123I]FP-CIT binding to dopamine transporters in rat frontal cortex and hippocampus

“…Therefore, reduced specific [ 123 I]FP-CIT binding, as observed in the present study after administration of methylphenidate in combination with quipazine, probably reflects changes in DA terminal markers. In addition, since [ 123 I]␤-CIT has higher binding ratios for the 5-HT transporter than [ 123 I]FP-CIT (Reneman et al, 1999), and no reductions were observed in [ 123 I]␤-CIT binding after administration of methylphenidate in addition to quipazine, it is likely that DA and not 5-HT terminal markers were affected.…”

“…Therefore, the combination of FP-CIT and these two radioligands was chosen to assess both the 5-HT and DA system. Two hours after injection of [ 123 I]FP-CIT (Booij et al, 1997) and 1 h after injection of [ 123 I]␤-CIT (Reneman et al, 1999), animals were killed by bleeding via heart puncture under ether anesthesia. The brains were quickly removed, dissected into frontal cortex, hippocampus, striatum, hypothalamus, and cerebellum, and weighed.…”

Age-dependent effects of chronic fluoxetine treatment on the serotonergic system one week following treatment

“…with approximately 1.85 MBq [ 123 I]β-CIT. Three hours after injection of [ 123 I]β-CIT (Reneman et al 1999), animals were killed by bleeding via heart puncture under isoflurane anesthesia. The brains were quickly removed and dissected into the following regions: prefrontal cortex, cingulated cortex, occipital cortex, hippocampus, hypothalamus, striatum, raphe area and cerebellum and weighed.…”

“…The brains were quickly removed and dissected into the following regions: prefrontal cortex, cingulated cortex, occipital cortex, hippocampus, hypothalamus, striatum, raphe area and cerebellum and weighed. The striatum was included as a negative, since [ 123 I]β-CIT uptake in this region reflects primarily binding to dopamine transporters (Reneman et al 1999). The 123 I radio activity of [ 123 I]β-CIT in each region was assayed with a gamma counter.…”

“…In this respect, we conducted explorative studies of ex vivo binding assays in various 5-HT-rich brain regions with a radioligand for SERT ([ 123 I]β-CIT (Reneman et al 1999) (experiment B), and phMRI with fluoxetine as an index of 5-HT availability and/or SERT functionality. It has been shown that the blood oxygenation level dependent (BOLD) signal is sensitive for changes in 5-HT itself (Preece et al 2009;McKie et al 2005;Schwarz et al 2007) and SERT function (Downey et al 2010) (experiment C).…”