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.
(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.
Brasić
James Robert
JR
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
Zhou
Yun
Y
Musachio
John L
JL
Hilton
John
J
Fan
Hong
H
Crabb
Andrew
A
Endres
Christopher J
CJ
Reinhardt
Melvin J
MJ
Dogan
Ahmet S
AS
Alexander
Mohab
M
Rousset
Olivier
O
Maris
Marika A
MA
Galecki
Jeffrey
J
Nandi
Ayon
A
Wong
Dean F
DF
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
C426745:5-iodo-3-(2-azetidinylmethoxy)pyridine; D001384:Azetidines; D007457:Iodine Radioisotopes; D011725:Pyridines