Synthesis and evaluation of iodinated TZTP-derivatives as potential radioligands for imaging of muscarinic M2 receptors with SPET.
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.
Knol
Remco J J
RJ
Graduate School of Neurosciences, Department of Nuclear Medicine, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands. r.j.knol@amc.uva.nl
Doornbos
Tamme
T
van den Bos
Jan C
JC
de Bruin
Kora
K
Pfaffendorf
Martin
M
Aanhaanen
Wim
W
Janssen
Anton G M
AG
Vekemans
Joseph A J M
JA
van Eck-Smit
Berthe L F
BL
Booij
Jan
J
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
D011725:Pyridines; D019275:Radiopharmaceuticals; D043585:Receptor, Muscarinic M2; D013830:Thiadiazoles