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

• 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
• ISSN: 0969-8051; 1872-9614
• DOI: 10.1016/j.nucmedbio.2004.09.007

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.