title: Single photon emission computed tomography experience with (S)-5-[(123)I]iodo-3-(2-azetidinylmethoxy)pyridine in the living human brain of smokers and nonsmokers.
abstract: (S)-5-[(123)I]iodo-3-(2-azetidinylmethoxy)pyridine (5-[(123)I]IA), a novel potent radioligand for high-affinity alpha4beta2* neuronal nicotinic acetylcholine receptors (nAChRs), provides a means to evaluate the density and the distribution of nAChRs in the living human brain. We sought in healthy adult smokers and nonsmokers to (1) evaluate the safety, tolerability, and efficacy of 5-[(123)I]IA in an open nonblind trial and (2) to estimate the density and the distribution of alpha(4)beta(2)* nAChRs in the brain. Single photon emission computed tomography (SPECT) was performed for 5 h after the i.v. administration of approximately 0.001 microg/kg ( approximately 10 mCi) 5-[(123)I]IA. Blood pressure, heart rate, and neurobehavioral status were monitored before, during, and after the administration of 5-[(123)I]IA to 12 healthy adults (8 men and 4 women) (6 smokers and 6 nonsmokers) ranging in age from 19 to 46 years (mean = 28.25, standard deviation = 8.20). High plasma-nicotine level was significantly associated with low 5-[(123)I]IA binding in: (1) the caudate head, the cerebellum, the cortex, and the putamen, utilizing both the Sign and Mann-Whitney U-tests; (2) the fusiform gyrus, the hippocampus, the parahippocampus, and the pons utilizing the Mann-Whitney U-test; and (3) the thalamus utilizing the Sign test. We conclude that 5-[(123)I]IA is a safe, well-tolerated, and effective pharmacologic agent for human subjects to estimate high-affinity alpha4/beta2 nAChRs in the living human brain.
authors.affiliation: Division of Nuclear Medicine, Russell H. Morgan Department of Radiology and Radiological Science, Johns Hopkins University School of Medicine, Baltimore, Maryland 21287, USA. brasic@jhmi.edu
authors.forename: James Robert
authors.initials: JR
authors.lastname: Brasić
authors.forename: Yun
authors.initials: Y
authors.lastname: Zhou
authors.forename: John L
authors.initials: JL
authors.lastname: Musachio
authors.forename: John
authors.initials: J
authors.lastname: Hilton
authors.forename: Hong
authors.initials: H
authors.lastname: Fan
authors.forename: Andrew
authors.initials: A
authors.lastname: Crabb
authors.forename: Christopher J
authors.initials: CJ
authors.lastname: Endres
authors.forename: Melvin J
authors.initials: MJ
authors.lastname: Reinhardt
authors.forename: Ahmet S
authors.initials: AS
authors.lastname: Dogan
authors.forename: Mohab
authors.initials: M
authors.lastname: Alexander
authors.forename: Olivier
authors.initials: O
authors.lastname: Rousset
authors.forename: Marika A
authors.initials: MA
authors.lastname: Maris
authors.forename: Jeffrey
authors.initials: J
authors.lastname: Galecki
authors.forename: Ayon
authors.initials: A
authors.lastname: Nandi
authors.forename: Dean F
authors.initials: DF
authors.lastname: Wong
mesh_terms: D000328:Adult; D001384:Azetidines / Q000378:metabolism*; D001921:Brain / Q000033:anatomy & histology / Q000000981:diagnostic imaging*; D001931:Brain Mapping; D005260:Female; D007839:Functional Laterality; D006801:Humans; D007457:Iodine Radioisotopes / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D011725:Pyridines / Q000378:metabolism*; D012907:Smoking / Q000378:metabolism*; D013997:Time Factors; D015899:Tomography, Emission-Computed, Single-Photon; D055815:Young Adult
chemical_list: C426745:5-iodo-3-(2-azetidinylmethoxy)pyridine; D001384:Azetidines; D007457:Iodine Radioisotopes; D011725:Pyridines