title: A novel technetium-99m radioligand for the 5-HT(1A) receptor derived from desmethyl-WAY-100635 (DWAY).
abstract: 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.
authors.affiliation: Forschungszentrum Rossendorf, Institut für Bioanorganische und Radiopharmazeutische Chemie, PF 510119, 01314 Dresden, Germany. i.heimbold@fz-rossendorf.de
authors.forename: Ilka
authors.initials: I
authors.lastname: Heimbold
authors.forename: Antje
authors.initials: A
authors.lastname: Drews
authors.forename: Rosemarie
authors.initials: R
authors.lastname: Syhre
authors.forename: Marion
authors.initials: M
authors.lastname: Kretzschmar
authors.forename: Hans-Jürgen
authors.initials: HJ
authors.lastname: Pietzsch
authors.forename: Bernd
authors.initials: B
authors.lastname: Johannsen
mesh_terms: D000818:Animals; D001345:Autoradiography; D001921:Brain / Q000000981:diagnostic imaging* / Q000378:metabolism*; D010879:Piperazines / Q000138:chemical synthesis / Q000493:pharmacokinetics; D011725:Pyridines / Q000138:chemical synthesis / Q000493:pharmacokinetics; D011877:Radionuclide Imaging; D019275:Radiopharmaceuticals / Q000138:chemical synthesis / Q000493:pharmacokinetics; D051381:Rats; D017208:Rats, Wistar; D044402:Receptor, Serotonin, 5-HT2A; D018340:Receptors, Adrenergic, alpha-1 / Q000032:analysis; D017448:Receptors, Dopamine D2 / Q000032:analysis; D011985:Receptors, Serotonin / Q000032:analysis*; D044263:Receptors, Serotonin, 5-HT1; D013667:Technetium / Q000493:pharmacokinetics; D014018:Tissue Distribution
chemical_list: D010879:Piperazines; D011725:Pyridines; D019275:Radiopharmaceuticals; D044402:Receptor, Serotonin, 5-HT2A; D018340:Receptors, Adrenergic, alpha-1; D017448:Receptors, Dopamine D2; D011985:Receptors, Serotonin; D044263:Receptors, Serotonin, 5-HT1; C112544:desmethyl-WAY 100635; D013667:Technetium