title: Synthesis and in vivo evaluation of a new PET radioligand for studying sigma-2 receptors.
abstract: The cyclohexyl piperazine 1 (1-cyclohexyl-4-[3-(5-methoxy-1,2,3,4-tetrahydro-naphthalen-1-yl)-propyl]-piperazine) has been shown to be a potent and selective sigma-2 receptor ligand. In the present study, we prepared [(11)C]1 by O-alkylation of the phenolic precursor 2 with [(11)C]CH(3)I. [(11)C]1 was obtained in a 29% non-decay corrected yield and specific activity of 9299 mCi/micromol calculated at end-of-synthesis. The biodistribution of [(11)C]1 in mouse brain demonstrated rapid and homogenous concentration in all brain structures, which included the cortex, thalamus, cerebellum and striatum. Co-administration of unlabelled 1 (1 mg/kg) or the sigma-2 selective ligand SM-21 (1 mg/kg) failed to show any significant inhibition of [(11)C]1 uptake in the mouse brain. The evaluation of this radioligand in vivo in the mouse clearly indicates that it does not possess the required properties for studying sigma-2 receptors in the brain using PET.
authors.affiliation: Department of PET and Nuclear Medicine, Royal Prince Alfred Hospital, Missenden Rd., Camperdown, NSW 2050, Australia. mkassiou@med.usyd.edu.au
authors.forename: Michael
authors.initials: M
authors.lastname: Kassiou
authors.forename: Robert F
authors.initials: RF
authors.lastname: Dannals
authors.forename: Xiang
authors.initials: X
authors.lastname: Liu
authors.forename: Dean F
authors.initials: DF
authors.lastname: Wong
authors.forename: Hayden T
authors.initials: HT
authors.lastname: Ravert
authors.forename: Ursula A
authors.initials: UA
authors.lastname: Scheffel
mesh_terms: D000818:Animals; D001921:Brain / Q000378:metabolism; D004353:Drug Evaluation, Preclinical; D051379:Mice; D009281:Naphthalenes / Q000378:metabolism / Q000493:pharmacokinetics*; D010879:Piperazines / Q000378:metabolism / Q000493:pharmacokinetics*; D049268:Positron-Emission Tomography; D011869:Radioligand Assay; D019275:Radiopharmaceuticals / Q000378:metabolism / Q000493:pharmacokinetics*; D017480:Receptors, sigma / Q000378:metabolism*; D014018:Tissue Distribution
chemical_list: C505382:1-cyclohexyl-4-(3-(5-methoxy-1,2,3,4-tetrahydro-naphthalen-1-yl)-propyl)-piperazine; D009281:Naphthalenes; D010879:Piperazines; D019275:Radiopharmaceuticals; D017480:Receptors, sigma