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 M 2 receptor subtype with SPET. One of these compounds, 5-(E)-iodopentenylthio-TZTP, has high in vitro affinity (K i = 4.9 nM) and moderate selectivity for the muscarinic M 2 receptor subtype. Although the uptake pattern in the biodistribution studies in rats is consistent with muscarinic M 2 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.