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 N₂S₂ 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 IC₅₀ value for the 5-HT_1A receptor of 1.29 nM against the selective 5-HT_1A agonist [³H]8-OH-DPAT, a moderate selectivity towards the alpha₁-adrenergic receptor (IC₅₀ of 8.1 nM against [³H]prazosin) and a good selectivity for the D₂ receptor (IC₅₀ of 192 nM against [³H]spiperone) and the 5-HT_2A receptor (IC₅₀ of 922 nM against [³H]ketanserin). Biodistribution studies in rats show an initial brain uptake of 0.65%±0.07% ID 2.5 min p.i. In vitro autoradiographic studies of the ^99mTc complex in rat brains indicate a strong specific accumulation of the radioactivity in 5-HT_1A receptor-rich brain regions.