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.…”

5‐HT radioligands for human brain imaging with PET and SPECT

“…Various analogues of β‐[ 123 I]CIT have been made through modest modifications of the structure, such as labelling at different positions and creation of fluoroalkyl analogues to decrease the time to reach pseudoequilibrium, but these efforts were mainly directed at improving its effectiveness for imaging the dopamine reuptake transporter (DAT). The development of nor‐β‐[ 123 I]CIT (2‐β‐carbomethoxy‐3‐β‐(4‐iodophenyl)nortropane) produced a radioligand with supposedly increased specific binding for SERT over DAT in humans, but it remains controversial whether nor ‐β‐[ 123 I]CIT is a better radioligand for SERT than β‐[ 123 I]CIT …”

“…The development of nor-b-[ 123 I]CIT (2-b-carbomethoxy-3-b-(4-iodophenyl)nortropane) 327,328 produced a radioligand with supposedly increased specific binding for SERT over DAT in humans, but it remains controversial whether nor-b-[ 123 I]CIT is a better radioligand for SERT than b-[ 123 I]CIT. 329 Today, several hundred publications (Table II shows 330,331 generalized anxiety disorder, 332 obsessive-compulsive disorder, 333 panic disorder, 334 and Parkinson's disease, 335 among others. The disadvantage of these SPECT ligands is their inability to selectively image SERT.…”

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.…”