title: 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.
abstract: 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 D3 receptors while its potential for sigma receptor imaging is severely hampered by its affinity for dopamine receptors.
authors.affiliation: Department of Radiopharmacy, Faculty of Pharmaceutical Sciences, Gent University, Harelbekestraat 72, B-9000 Gent, Belgium. ludovicus.staelens@ugent.be
authors.forename: Ludovicus
authors.initials: L
authors.lastname: Staelens
authors.forename: Ruth
authors.initials: R
authors.lastname: Oltenfreiter
authors.forename: Filip
authors.initials: F
authors.lastname: Dumont
authors.forename: Rikki N
authors.initials: RN
authors.lastname: Waterhouse
authors.forename: Katia
authors.initials: K
authors.lastname: Vandenbulcke
authors.forename: Peter
authors.initials: P
authors.lastname: Blanckaert
authors.forename: Rudi A
authors.initials: RA
authors.lastname: Dierckx
authors.forename: Guido
authors.initials: G
authors.lastname: Slegers
mesh_terms: D000818:Animals; D001549:Benzamides / Q000493:pharmacokinetics; D001921:Brain / Q000000981:diagnostic imaging* / Q000378:metabolism*; D005240:Feasibility Studies; D008297:Male; D008657:Metabolic Clearance Rate; D051379:Mice; D009928:Organ Specificity; D010879:Piperazines / Q000493:pharmacokinetics; D011817:Rabbits; D019275:Radiopharmaceuticals / Q000493:pharmacokinetics; D017480:Receptors, sigma / Q000378:metabolism*; D013045:Species Specificity; D014018:Tissue Distribution; D015899:Tomography, Emission-Computed, Single-Photon / Q000379:methods*
chemical_list: C503389:4-iodo-N-(4-(4-(2-methoxyphenyl)-piperazin-1-yl)butyl)-benzamide; D001549:Benzamides; D010879:Piperazines; D019275:Radiopharmaceuticals; D017480:Receptors, sigma