TY - JOUR T1 - In Vivo Imaging of Human Cerebral Nicotinic Acetylcholine Receptors with 2-<sup>18</sup>F-Fluoro-A-85380 and PET JF - Journal of Nuclear Medicine JO - J Nucl Med SP - 240 LP - 247 VL - 46 IS - 2 AU - Jean-Dominique Gallezot AU - Michel Bottlaender AU - Marie-Claude Grégoire AU - Dimitri Roumenov AU - Jean-Robert Deverre AU - Christine Coulon AU - Michèle Ottaviani AU - Frédéric Dollé AU - André Syrota AU - Héric Valette Y1 - 2005/02/01 UR - http://jnm.snmjournals.org/content/46/2/240.abstract N2 - 2-18F-Fluoro-3-[2(S)-2-azetidinylmethoxy]pyridine (2-18F-fluoro-A-85380) is a PET radioligand that is specific for nicotinic acetylcholine receptors (nAChRs) and has a high affinity for the α4β2 subtype. The purpose of this study was to evaluate different strategies to quantify 2-18F-fluoro-A-85380 binding in healthy nonsmoking human volunteers. Methods: After intravenous injection of 189 ± 30 MBq (0.8–5.7 nmol) of 2-18F-fluoro-A-85380, the first dynamic PET scan was acquired over 150 min. The second 30-min PET scan was performed 60 min later. Time–activity curves were generated from volumes of interest. 2-18F-Fluoro-A-85380 volume of distribution (DV) was quantified using compartmental kinetic analysis and Logan graphical analysis. In the kinetic analysis, the 1-tissue compartment model (1TCM) and the 2-tissue (2TCM) compartment model were applied. The most appropriate kinetic model was determined using the Akaike Information Criterion. The effect of reducing the PET study duration on the reliability of the DV values computed by the kinetic and the graphical analyses was evaluated. Results: Time–activity curves were better described by the 2TCM. The DV values ranged from 5.2 ± 0.5 in the occipital cortex, 6.2 ± 0.2 in the frontal cortex, and 7.3 ± 0.4 in the putamen to 15.4 ± 2.1 in the thalamus. These regional DV values were consistent with the distribution of nAChRs in the human brain. Logan graphical analysis provided slightly lower DV values than those of the 2TCM (from −3.5% in the occipital cortex to −6.6% in the thalamus). The minimal study duration required to obtain stable DV estimates in all regions was similar for the 2 methods: 140 min for the 2TCM and 150 min for the Logan analysis. DV estimates obtained with the 2TCM were more stable than those calculated by the Logan approach for the same scan duration. Conclusion: These results show that 2-18F-fluoro-A-85380 can be used to assess nAChRs binding in the human brain with PET. ER -