title: Synthesis and evaluation of iodinated TZTP-derivatives as potential radioligands for imaging of muscarinic M2 receptors with SPET.
abstract: A series of iodinated thiadiazolyltetrahydro-1-methyl-pyridine (TZTP) compounds was synthesized and evaluated in vitro and in vivo as potential radioligands for imaging of the muscarinic M2 receptor subtype with SPET. One of these compounds, 5-(E)-iodopentenylthio-TZTP, has high in vitro affinity (Ki = 4.9 nM) and moderate selectivity for the muscarinic M2 receptor subtype. Although the uptake pattern in the biodistribution studies in rats is consistent with muscarinic M2 receptor disribution, specific in vivo binding to these receptors could not be demonstrated. The usefulness of this tracer in human SPET imaging may therefore be limited.
authors.affiliation: Graduate School of Neurosciences, Department of Nuclear Medicine, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands. r.j.knol@amc.uva.nl
authors.forename: Remco J J
authors.initials: RJ
authors.lastname: Knol
authors.forename: Tamme
authors.initials: T
authors.lastname: Doornbos
authors.forename: Jan C
authors.initials: JC
authors.lastname: van den Bos
authors.forename: Kora
authors.initials: K
authors.lastname: de Bruin
authors.forename: Martin
authors.initials: M
authors.lastname: Pfaffendorf
authors.forename: Wim
authors.initials: W
authors.lastname: Aanhaanen
authors.forename: Anton G M
authors.initials: AG
authors.lastname: Janssen
authors.forename: Joseph A J M
authors.initials: JA
authors.lastname: Vekemans
authors.forename: Berthe L F
authors.initials: BL
authors.lastname: van Eck-Smit
authors.forename: Jan
authors.initials: J
authors.lastname: Booij
mesh_terms: D000818:Animals; D005240:Feasibility Studies; D008297:Male; D008657:Metabolic Clearance Rate; D009928:Organ Specificity; D011725:Pyridines / Q000737:chemistry / Q000493:pharmacokinetics*; D019275:Radiopharmaceuticals / Q000138:chemical synthesis / Q000493:pharmacokinetics; D051381:Rats; D017208:Rats, Wistar; D043585:Receptor, Muscarinic M2 / Q000378:metabolism*; D013830:Thiadiazoles / Q000737:chemistry / Q000493:pharmacokinetics*; D014018:Tissue Distribution
chemical_list: D011725:Pyridines; D019275:Radiopharmaceuticals; D043585:Receptor, Muscarinic M2; D013830:Thiadiazoles