title: Novel technetium ligands with affinity for the muscarinic cholinergic receptor.
abstract: The synthesis and preliminary biological characterization of two isomeric technetium labeled complexes (2,5,5,9-tetramethyl-4,7-diaza-7-(3' (R)-quinuclidinylcarboxymethyl)-2,9-decanedithiolato oxo 99/99mtechnetium(V), [99/99mTc]-1 and [99/99mTc]-2) designed to exhibit affinity to muscarinic cholinergic receptors are described. In vitro binding assays were conducted in mouse brain homogenates (whole brain-cerebellum) at 37 degrees C by the centrifugation method, where non-specific binding was defined by atropine (1 microM). The measured affinity (KD) of [99Tc]-1 for mAChR was 1.9 +/- 0.5 microM (mean +/- SEM; n = 3) and [99Tc]-2 was 4.5 +/- 0.5 microM (mean +/- SEM; n = 3). Scatchard analysis indicated that Bmax values were 10.6 +/- 0.5 and 16.9 +/- 0.5 pmol/mg tissue, respectively. In competition assays, [99Tc]-1 exhibited an apparent affinity (KI) of 16.5 microM (n = 2) against [125I] iododexetimide, whereas [99Tc]-2 exhibited an affinity (KI) of 105 microM. In vivo, 0.3% of the injected dose of [99mTc]-1 and [99mTc]-2 accumulated in the brain at 5 min after injection. These values indicate technetium analogues of neuroreceptor binding ligands can be synthesized and retain some affinity for the receptor.
authors.affiliation: Department of Environmental Health Sciences, Johns Hopkins University School of Hygiene and Public Health, Baltimore, MD 21205-2179, USA.
authors.forename: S Z
authors.initials: SZ
authors.lastname: Lever
authors.forename: K E
authors.initials: KE
authors.lastname: Baidoo
authors.forename: A
authors.initials: A
authors.lastname: Mahmood
authors.forename: K
authors.initials: K
authors.lastname: Matsumura
authors.forename: U
authors.initials: U
authors.lastname: Scheffel
authors.forename: H N
authors.initials: HN
authors.lastname: Wagner
mesh_terms: D000818:Animals; D001667:Binding, Competitive; D001812:Blood-Brain Barrier / Q000502:physiology*; D018360:Crystallography, X-Ray; D008024:Ligands; D016014:Linear Models; D008297:Male; D051379:Mice; D008815:Mice, Inbred Strains; D008958:Models, Molecular; D015609:Organotechnetium Compounds / Q000378:metabolism*; D011976:Receptors, Muscarinic / Q000378:metabolism*; D013237:Stereoisomerism; D014018:Tissue Distribution
chemical_list: D008024:Ligands; D015609:Organotechnetium Compounds; D011976:Receptors, Muscarinic