title: Quantification of nicotinic acetylcholine receptors in human brain using [123I]5-I-A-85380 SPET.
abstract: The purpose of this study was to assess the utility of a new single-photon emission tomography ligand, [123I]5-iodo-3-[2(S)-2-azetidinylmethoxy]pyridine (5-I-A-85380), to measure regional nAChR binding in human brain. Six healthy nonsmoker subjects (two men and four women, age 33 +/- 15 years) participated in both a bolus (dose: 317 +/- 42 MBq) and a bolus plus constant infusion (dose of bolus: 98 +/- 32 MBq, B/I=6.7 +/- 2.6 h, total dose: 331 +/- 55 MBq) study. The study duration was 5-8 h and 14 h in the former and the latter, respectively. Nonlinear least-squares compartmental analysis was applied to bolus studies to calculate total (VT') and specific (VS') distribution volumes. A two-tissue compartment model was applied to identify VS'. VT' was also calculated in B/I studies. In bolus studies, VT' was well identified by both one- and two-tissue compartment models, with a coefficient of variation of less than 5% in most regions. The two-compartment model gave VT' values of 51, 22, 27, 32, 20, 19, 20, and 17 ml cm(-3) in thalamus, cerebellum, putamen, pons, and frontal, parietal, temporal, and occipital cortices, respectively. The two-compartment model did not identify VS' well. B/I studies provided poor accuracy of VT' measurement, possibly due to deviations from equilibrium conditions. These results demonstrate the feasibility of quantifying high-affinity type nAChRs using [123I]5-I-A-85380 in humans and support the use of VT' measured by bolus studies.
authors.affiliation: Molecular Imaging Branch, National Institute of Mental Health, Bethesda, MD 20892-0135, USA. FujitaM@intra.nimh.nih.gov
authors.forename: Masahiro
authors.initials: M
authors.lastname: Fujita
authors.forename: Masanori
authors.initials: M
authors.lastname: Ichise
authors.forename: Christopher H
authors.initials: CH
authors.lastname: van Dyck
authors.forename: Sami S
authors.initials: SS
authors.lastname: Zoghbi
authors.forename: Gilles
authors.initials: G
authors.lastname: Tamagnan
authors.forename: Alexey G
authors.initials: AG
authors.lastname: Mukhin
authors.forename: Ali
authors.initials: A
authors.lastname: Bozkurt
authors.forename: Nicholas
authors.initials: N
authors.lastname: Seneca
authors.forename: Dnyanesh
authors.initials: D
authors.lastname: Tipre
authors.forename: Christopher C
authors.initials: CC
authors.lastname: DeNucci
authors.forename: Hidehiro
authors.initials: H
authors.lastname: Iida
authors.forename: D Bruce
authors.initials: DB
authors.lastname: Vaupel
authors.forename: Andrew G
authors.initials: AG
authors.lastname: Horti
authors.forename: Andrei O
authors.initials: AO
authors.lastname: Koren
authors.forename: Alane S
authors.initials: AS
authors.lastname: Kimes
authors.forename: Edythe D
authors.initials: ED
authors.lastname: London
authors.forename: John P
authors.initials: JP
authors.lastname: Seibyl
authors.forename: Ronald M
authors.initials: RM
authors.lastname: Baldwin
authors.forename: Robert B
authors.initials: RB
authors.lastname: Innis
mesh_terms: D000328:Adult; D001384:Azetidines / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics*; D001921:Brain / Q000000981:diagnostic imaging* / Q000378:metabolism*; D005260:Female; D006801:Humans; D007090:Image Interpretation, Computer-Assisted / Q000379:methods*; D007262:Infusions, Intravenous; D007275:Injections, Intravenous; D008297:Male; D008657:Metabolic Clearance Rate; D008954:Models, Biological; D011725:Pyridines / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics*; D019275:Radiopharmaceuticals / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics; D011950:Receptors, Cholinergic / Q000378:metabolism*; D015203:Reproducibility of Results; D012680:Sensitivity and Specificity; D014018:Tissue Distribution; D015899:Tomography, Emission-Computed, Single-Photon / Q000379:methods*
chemical_list: C426745:5-iodo-3-(2-azetidinylmethoxy)pyridine; D001384:Azetidines; D011725:Pyridines; D019275:Radiopharmaceuticals; D011950:Receptors, Cholinergic