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

Abstract

Gamma-aminobutyric acid (GABA)A/benzodiazepine (BZ) receptor chloride channel consists of several subunits. The diversity of the α subunits results in the various ligand selectivity and functionally different properties of the GABAA/BZ receptor. Although [¹¹C] Ro15-4513 is reported to be a radioligand that has relatively high affinity for α5 subunit-containing GABAA/BZ receptor, it remained to be evaluated fully. The aim of this study was to evaluate the quantitative analyses of [¹¹C]Ro15-4513 in the living human brain. Positron emission tomography examinations were performed in eight healthy male volunteers after intravenous injection of [¹¹C]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. The accumulation of [¹¹C]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. The reference tissue methods using pons as a reference region can be used for quantitative analysis of [¹¹C]Ro15-4513 binding. SRTM seemed less susceptible to noise than does graphical analysis.