TY - JOUR
T1 - Quantification of nicotinic acetylcholine receptors in human brain using [123I]5-I-A-85380 SPET
AU - Fujita, Masahiro
AU - Ichise, Masanori
AU - Van Dyck, Christopher H.
AU - Zoghbi, Sami S.
AU - Tamagnan, Gilles
AU - Mukhin, Alexey G.
AU - Bozkurt, Ali
AU - Seneca, Nicholas
AU - Tipre, Dnyanesh
AU - DeNucci, Christopher C.
AU - Iida, Hidehiro
AU - Vaupel, D. Bruce
AU - Horti, Andrew G.
AU - Koren, Andrei O.
AU - Kimes, Alane S.
AU - London, Edythe D.
AU - Seibyl, John P.
AU - Baldwin, Ronald M.
AU - Innis, Robert B.
N1 - Funding Information:
Acknowledgements. The authors thank C. Burger, PhD, P. Rudnicki, PhD, K. Mikolajczyk, PhD, M. Grodzki, PhD, and M. Szabatin, PhD for providing PMOD 2.50; Asahi Kasei Information Systems Co., Ltd for providing Dr. View 4.0, which assisted analysis with scatter correction; L. Amici, S. Giddings, G. Morano, A, Perez, Q. Ramsby, N Sheung, and E. Smith for technical assistance; and Girma Hawariat, PhD, for statistical analysis. This work was supported by the Connecticut/Massachusetts VA Mental Illness Research Education and Clinical Center and Transdisciplinary Tobacco Research Center P50 DA84733.
Copyright:
Copyright 2008 Elsevier B.V., All rights reserved.
PY - 2003/12
Y1 - 2003/12
N2 - 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. Non-linear least-squares compartmental analysis was applied to bolus studies to calculate total (VT′) and specific (V S′) 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.
AB - 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. Non-linear least-squares compartmental analysis was applied to bolus studies to calculate total (VT′) and specific (V S′) 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.
KW - Compartmental modeling
KW - Distribution volume
KW - Equilibrium
KW - High-affinity type nicotinic receptors
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UR - http://www.scopus.com/inward/citedby.url?scp=0346103816&partnerID=8YFLogxK
U2 - 10.1007/s00259-003-1320-0
DO - 10.1007/s00259-003-1320-0
M3 - Article
C2 - 14523584
AN - SCOPUS:0346103816
SN - 1619-7070
VL - 30
SP - 1620
EP - 1629
JO - European Journal of Nuclear Medicine and Molecular Imaging
JF - European Journal of Nuclear Medicine and Molecular Imaging
IS - 12
ER -