IN-VIVO STUDIES WITH [I-125] 5-I-A-85380, A NICOTINIC ACETYLCHOLINE-RECEPTOR RADIOLIGAND

5-[I-125]iodo-3-(2(S)-azetidinylmethoxy)pyridine ([I-125]5-I-A-85380) was evaluated in the mouse as a potential in vivo imaging ligand for c entral nicotinic acetylcholine receptors (nAChRs). After i.v. administ ration of [I-125]5-I-A-85380, peak brain levels of radioactivity were measured within 1 h and declined slowly over 4 h. [I-125]5-I-A-85380 b inding 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 alpha 4 beta 2 nAChR agonist binding sites. The thalamus:cerebellum radioactivity ra tio, a measure of specific labeling, reached 37. Therefore, radiolabel ed 5-I-A-85380 has excellent potential as an imaging radiotracer for n AChRs, particularly with single photon emission computed tomography, w hen I-123 is incorporated into the molecule. NeuroReport 9: 2311-2317 (C) 1998 Rapid Science Ltd.