title: A novel nicotinic acetylcholine receptor antagonist radioligand for PET studies.
abstract: Using positron emission tomography (PET) with a specific and selective radioligand targeting nicotinic acetylcholine receptor (nAChR) would allow us to better understand various nAChR related CNS disorders. The use of radiolabeled nAChR antagonists would provide a much safer pharmacological profile, avoiding most peripheral side effects that might be generated from radiolabeled nAChR agonists even at the tracer level; thus, PET imaging with nAChR antagonists would facilitate clinical application. A potent and selective nAChR antagonist was labeled and characterized with PET in non-human primates. Its high brain uptake, high signal-to-noise ratio, and high specific binding strongly suggest a great potential to carry out imaging studies in humans. In addition, the use of a C-11 radiotracer would allow us to perform multiple PET studies in the same individual within a short time frame. The presence of an iodine atom in the molecule also allows the possibility to label with radioiodine for SPECT studies.
authors.affiliation: Chemistry Department, Brookhaven National Laboratory, Upton, NY 11973, USA. ding@bnl.gov
authors.forename: Yu-Shin
authors.initials: YS
authors.lastname: Ding
authors.forename: Kun-eek
authors.initials: KE
authors.lastname: Kil
authors.forename: Kuo-Shyan
authors.initials: KS
authors.lastname: Lin
authors.forename: Wei
authors.initials: W
authors.lastname: Ma
authors.forename: Yasuno
authors.initials: Y
authors.lastname: Yokota
authors.forename: Ivy F
authors.initials: IF
authors.lastname: Carroll
mesh_terms: D000818:Animals; D001667:Binding, Competitive / Q000187:drug effects; D001921:Brain / Q000000981:diagnostic imaging* / Q000187:drug effects; D019086:Bridged Bicyclo Compounds, Heterocyclic / Q000138:chemical synthesis / Q000737:chemistry / Q000493:pharmacokinetics*; D002250:Carbon Radioisotopes; D004353:Drug Evaluation, Preclinical; D008024:Ligands; D015394:Molecular Structure; D009538:Nicotine / Q000493:pharmacokinetics; D018733:Nicotinic Antagonists / Q000138:chemical synthesis / Q000737:chemistry / Q000493:pharmacokinetics*; D010215:Papio; D049268:Positron-Emission Tomography / Q000379:methods*; D011978:Receptors, Nicotinic / Q000187:drug effects*; D013329:Structure-Activity Relationship; D013997:Time Factors
chemical_list: C509758:7-methyl-2-exo-(3'-iodo-5'-pyridinyl)-7-azabicyclo(2.2.1)heptane; D019086:Bridged Bicyclo Compounds, Heterocyclic; D002250:Carbon Radioisotopes; D008024:Ligands; D018733:Nicotinic Antagonists; D011978:Receptors, Nicotinic; D009538:Nicotine