In Vivo Imaging of Human Cerebral Nicotinic Acetylcholine Receptors with 2-18F-Fluoro-A-85380 and PET

Journal of Nuclear Medicine

Héric Valette¹  Jean-Robert Deverre¹  Marie-Claude Grégoire¹  Michèle Ottaviani¹  André Syrota¹  Jean-Dominique Gallezot¹  Christine Coulon¹  Dimitri Roumenov¹  Michel Bottlaender¹  Frédéric Dollé¹ 

关键词: 2-¹⁸F-fluoro-A-85380;    PET;    nicotinic receptors;    human brain;    distribution volume;   

DOI  :  

学科分类：医学（综合）

来源: Society of Nuclear Medicine

【 摘 要 】

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.

【 授权许可】

Unknown