Date: 02 Oct 2003

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.