Design and biological evaluation of ^99mTc-ligands derived from WAY 100,635 and D.WAY for serotonin-5-HT_1A and alpha1-adrenergic receptor binding

Novel Tc-labelled receptor ligands for the serotonin 5HT_1A receptor have been synthesized and biologically evaluated. The complexes consist of a Tc chelate unit with the metal at the oxidation state +5 or +3 and 1-(2-methoxyphenyl)-piperazine or 2-(1-piperazino)phenol as receptor-targeting domain. Tc chelate and receptor targeting moiety are linked by an alkylspacer of various chain length. Re was used as Tc surrogate for complete chemical characterization and in vitro receptor-binding studies. All complexes display subnanomolar affinities for the 5-HT_1A receptor but also high affinities for the alpha1-adrenergic receptor. Biodistribution studies in rats show initial brain uptakes between 0.2% ID and 0.6% ID five minutes post injection. In vitro autoradiographic studies in rat brain and post-mortem human brain indicate the accumulation of the Tc-99m complexes in areas which are rich in 5-HT_1A receptors and additionally in areas rich in alpha1-adrenergic receptors.