Quantification of nicotinic acetylcholine receptors in human brain using [123I]5-I-A-85380 SPET.
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.
Fujita
Masahiro
M
Molecular Imaging Branch, National Institute of Mental Health, Bethesda, MD 20892-0135, USA. FujitaM@intra.nimh.nih.gov
Ichise
Masanori
M
van Dyck
Christopher H
CH
Zoghbi
Sami S
SS
Tamagnan
Gilles
G
Mukhin
Alexey G
AG
Bozkurt
Ali
A
Seneca
Nicholas
N
Tipre
Dnyanesh
D
DeNucci
Christopher C
CC
Iida
Hidehiro
H
Vaupel
D Bruce
DB
Horti
Andrew G
AG
Koren
Andrei O
AO
Kimes
Alane S
AS
London
Edythe D
ED
Seibyl
John P
JP
Baldwin
Ronald M
RM
Innis
Robert B
RB
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*
C426745:5-iodo-3-(2-azetidinylmethoxy)pyridine; D001384:Azetidines; D011725:Pyridines; D019275:Radiopharmaceuticals; D011950:Receptors, Cholinergic