In vivo evaluation of [ 123I]-4-iodo- N-(4-(4-(2-methoxyphenyl)-piperazin-1-yl)butyl)-benzamide: a potential sigma receptor ligand for SPECT studies

In this study, in vivo evaluation in mice and rabbits of [ 123I]-4-iodo- N-(4-(4-(2-methoxyphenyl)-piperazin-1-yl)butyl)-benzamide ([ 123I]-BPB), a potential radioligand for visualisation of the sigma receptor by single photon emission computed tomography (SPECT), is reported. The compound possesses...

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Bibliographic Details
Published in:Nuclear medicine and biology 2005-02, Vol.32 (2), p.193-200
Main Authors: Staelens, Ludovicus, Oltenfreiter, Ruth, Dumont, Filip, Waterhouse, Rikki N., Vandenbulcke, Katia, Blanckaert, Peter, Dierckx, Rudi A., Slegers, Guido
Format: Article
Language:English
Subjects:
123I
Animals
Benzamides - pharmacokinetics
Brain - diagnostic imaging
Brain - metabolism
Dopamine D 3 receptors SPECT
Feasibility Studies
Male
Metabolic Clearance Rate
Mice
Organ Specificity
Piperazines - pharmacokinetics
Rabbits
Radiopharmaceuticals - pharmacokinetics
Receptors, sigma - metabolism
Sigma receptors
Species Specificity
Tissue Distribution
Tomography, Emission-Computed, Single-Photon - methods
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Summary:In this study, in vivo evaluation in mice and rabbits of [ 123I]-4-iodo- N-(4-(4-(2-methoxyphenyl)-piperazin-1-yl)butyl)-benzamide ([ 123I]-BPB), a potential radioligand for visualisation of the sigma receptor by single photon emission computed tomography (SPECT), is reported. The compound possesses appropriate lipophilicity (log P=2.2) and binds sigma-1 and sigma-2 receptors (pKi=6.51 and 6.79, respectively). In mice, this new radioiodinated tracer exhibited high brain uptake (4.99% ID/g tissue at 10 min postinjection) and saturable binding (3.06% ID/g tissue at 10 min postinjection) as determined by pretreatment with unlabeled [ 123I]-BPB. A metabolite study demonstrated no (less than 5%) labeled metabolites in the brain. In rabbits, regional brain distribution was investigated and the tracer displayed high, homogeneous central nervous system uptake. Selectivity was assessed by competition experiments with known sigma ligands. Metabolite analysis showed no (less than 8%) labeled metabolites in the rabbit brain. In conclusion, our findings indicate that [ 123I]-BPB is not a suitable tracer for visualisation of D 3 receptors while its potential for sigma receptor imaging is severely hampered by its affinity for dopamine receptors.
ISSN:0969-8051
1872-9614
DOI:10.1016/j.nucmedbio.2004.09.007