Quantitative analyses of [11C]Ro15-4513 binding to subunits of GABAA/benzodiazepine receptor in the living human brain

Background Gamma-aminobutyric acid (GABA)(A)/benzodiazepine (BZ) receptor chloride channel consists of several subunits. The diversity of the alpha subunits results in the various ligand selectivity and functionally different properties of the GABA(A)/BZ receptor. Although [C-11] Ro15-4513 is reported to be a radioligand that has relatively high affinity for alpha 5 subunit-containing GABA(A)/BZ receptor, it remained to be evaluated fully. Aim The aim of this study was to evaluate the quantitative analyses of [C-11]Ro15-4513 in the living human brain. Methods Positron emission tomography examinations were performed in eight healthy male volunteers after intravenous injection of [C-11]Ro15-4513. Kinetic analysis of data was performed with the two-compartment and three-compartment models using arterial input function. Linear graphical analysis and the simplified reference tissue model analysis (SRTM) were also performed using Pons as a reference region. In a simulation study, the effects of noise to the estimation of binding potentials were evaluated. Results The accumulation of [C-11]Ro15-4513 in the limbic system was relatively higher than in other cortex. The bindings were well described by the three-compartment model in the regions with specific binding. Binding potentials obtained from the graphical method and SRTM correlated well with those obtained from the three-compartment model. In the simulation study, estimated parameters from SRTM were less affected by noise compared with those from the graphical method. Conclusion The reference tissue methods using pons as a reference region can be used for quantitative analysis of [C-11]Ro15-4513 binding. SRTM seemed less susceptible to noise than does graphical analysis. Nucl Med Commun 30:872-880 (C) 2009 Wolters Kluwer Health | Lippincott Williams & Wilkins.