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Quantification of nicotinic acetylcholine receptors in human brain using [123I]5-I-A-85380 SPET

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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 (V T ′) and specific (V S ′) distribution volumes. A two-tissue compartment model was applied to identify V S ′. V T ′ was also calculated in B/I studies. In bolus studies, V T ′ 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 V T ′ 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 V S ′ well. B/I studies provided poor accuracy of V T ′ 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 V T ′ measured by bolus studies.

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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.

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Correspondence to Masahiro Fujita.

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Fujita, M., Ichise, M., van Dyck, C.H. et al. Quantification of nicotinic acetylcholine receptors in human brain using [123I]5-I-A-85380 SPET. Eur J Nucl Med Mol Imaging 30, 1620–1629 (2003). https://doi.org/10.1007/s00259-003-1320-0

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