In vivo studies with [125I]5-I-A-85380, a nicotinic acetylcholine receptor radioligand.
5-[125I]iodo-3-(2(S)-azetidinylmethoxy)pyridine ([125I]5-I-A-85380) was evaluated in the mouse as a potential in vivo imaging ligand for central nicotinic acetylcholine receptors (nAChRs). After i.v. administration of [125I]5-I-A-85380, peak brain levels of radioactivity were measured within 1 h and declined slowly over 4 h. [125I]5-I-A-85380 binding was saturable, and both its pharmacology, based upon inhibition studies, and its pattern of accumulation in brain regions having high nAChR densities were consistent with an interaction at alpha4beta2 nAChR agonist binding sites. The thalamus:cerebellum radioactivity ratio, a measure of specific labeling, reached 37. Therefore, radiolabeled 5-I-A-85380 has excellent potential as an imaging radiotracer for nAChRs, particularly with single photon emission computed tomography, when 123I is incorporated into the molecule.
Brain Imaging Center, Intramural Research Program, National Institute on Drug Abuse, Baltimore, MD 21224, USA.
D B
DB
Vaupel
A G
AG
Mukhin
A S
AS
Kimes
A G
AG
Horti
A O
AO
Koren
E D
ED
London
D000818:Animals; D001345:Autoradiography; D001384:Azetidines / Q000493:pharmacokinetics / Q000494:pharmacology*; D001522:Behavior, Animal / Q000187:drug effects; D001921:Brain / Q000378:metabolism; D018680:Cholinergic Antagonists / Q000494:pharmacology; D007457:Iodine Radioisotopes; D008024:Ligands; D008297:Male; D051379:Mice; D011869:Radioligand Assay; D011978:Receptors, Nicotinic / Q000187:drug effects*; D012640:Seizures / Q000139:chemically induced; D014018:Tissue Distribution; D015899:Tomography, Emission-Computed, Single-Photon
C104288:A 85380; D001384:Azetidines; D018680:Cholinergic Antagonists; D007457:Iodine Radioisotopes; D008024:Ligands; D011978:Receptors, Nicotinic