A novel technetium-99m radioligand for the 5-HT(1A) receptor derived from desmethyl-WAY-100635 (DWAY).

This paper reports the synthesis, biological evaluation and in vitro autoradiography of a new technetium-99m radioligand with high affinity for the 5-HT(1A) receptor. The neutral complex combines an N(2)S(2) diamine dithiol (DADT) ligand as complexing moiety for oxotechnetium(V) and a 2-(1-piperazino)phenol via a 6-carbon alkyl chain, derived from desmethyl-WAY 100635 (DWAY). The complex displays an IC(50) value for the 5-HT(1A) receptor of 1.29 n M against the selective 5-HT(1A) agonist [(3)H]8-OH-DPAT, a moderate selectivity towards the alpha(1)-adrenergic receptor (IC(50) of 8.1 n M against [(3)H]prazosin) and a good selectivity for the D(2) receptor (IC(50) of 192 n M against [(3)H]spiperone) and the 5-HT(2A)receptor (IC(50) of 922 n M against [(3)H]ketanserin). Biodistribution studies in rats show an initial brain uptake of 0.56%+/-0.07% ID 2.5 min p.i. In vitro autoradiographic studies of the (99m)Tc complex in rat brains indicate a strong specific accumulation of the radioactivity in 5-HT(1A) receptor-rich brain regions.