TY - JOUR
T1 - Single photon emission computed tomography experience with (S)-5-[ 123I]iodo-3-(2-azetidinylmethoxy)pyridine in the living human brain of smokers and nonsmokers
AU - Brašić, James Robert
AU - Zhou, Yun
AU - Musachio, John L.
AU - Hilton, John
AU - Fan, Hong
AU - Crabb, Andrew
AU - Endres, Christopher J.
AU - Reinhardt, Melvin J.
AU - Dogan, Ahmet S.
AU - Alexander, Mohab
AU - Rousset, Olivier
AU - Maris, Marika A.
AU - Galecki, Jeffrey
AU - Nandi, Ayon
AU - Wong, Dean F.
PY - 2009/4
Y1 - 2009/4
N2 - (S)-5-[123I]iodo-3-(2-azetidinylmethoxy)pyridine (5-[ 123I]IA), a novel potent radioligand for high-affinity α4β2* 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-[123I]IA in an open nonblind trial and (2) to estimate the density and the distribution of α4β2* nAChRs in the brain. Single photon emission computed tomography (SPECT) was performed for 5 h after the i.v. administration of ∼0.001 lg/kg (∼10 mCi) 5-[123I]IA. Blood pressure, heart rate, and neurobehavioral status were monitored before, during, and after the administration of 5-[123I]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-[123I]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-[123I]IA is a safe, well-tolerated, and effective pharmacologic agent for human subjects to estimate high-affinity α4/β2 nAChRs in the living human brain.
AB - (S)-5-[123I]iodo-3-(2-azetidinylmethoxy)pyridine (5-[ 123I]IA), a novel potent radioligand for high-affinity α4β2* 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-[123I]IA in an open nonblind trial and (2) to estimate the density and the distribution of α4β2* nAChRs in the brain. Single photon emission computed tomography (SPECT) was performed for 5 h after the i.v. administration of ∼0.001 lg/kg (∼10 mCi) 5-[123I]IA. Blood pressure, heart rate, and neurobehavioral status were monitored before, during, and after the administration of 5-[123I]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-[123I]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-[123I]IA is a safe, well-tolerated, and effective pharmacologic agent for human subjects to estimate high-affinity α4/β2 nAChRs in the living human brain.
KW - Binding
KW - Density
KW - Distribution
KW - Infusions
KW - Safety
KW - Tomography
KW - Treatment efficacy
UR - http://www.scopus.com/inward/record.url?scp=63049095919&partnerID=8YFLogxK
U2 - 10.1002/syn.20611
DO - 10.1002/syn.20611
M3 - Article
C2 - 19140167
AN - SCOPUS:63049095919
SN - 0887-4476
VL - 63
SP - 339
EP - 358
JO - Synapse
JF - Synapse
IS - 4
ER -