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 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.


OBJECTIVE
The aim of this study was to evaluate the quantitative analyses of [¹¹C]Ro15-4513 in the living human brain.


METHODS
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.


RESULTS
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.


CONCLUSIONS
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.
Asai
Yoshiyuki
Y
Molecular Neuroimaging Group, Molecular Imaging Center, National Institute of Radiological Sciences, Chiba, Japan.
Ikoma
Yoko
Y
Takano
Akihiro
A
Maeda
Jun
J
Toyama
Hinako
H
Yasuno
Fumihiko
F
Ichimiya
Tetsuya
T
Ito
Hiroshi
H
Suhara
Tetsuya
T
D000328:Adult; D001386:Azides / Q000378:metabolism*; D001569:Benzodiazepines / Q000378:metabolism*; D001921:Brain / Q000000981:diagnostic imaging / Q000378:metabolism*; D002250:Carbon Radioisotopes; D006801:Humans; D007700:Kinetics; D008297:Male; D049268:Positron-Emission Tomography; D011485:Protein Binding; D021122:Protein Subunits / Q000378:metabolism; D011963:Receptors, GABA-A / Q000378:metabolism*; D014022:Tissue Survival; D055815:Young Adult
D001386:Azides; D002250:Carbon Radioisotopes; D021122:Protein Subunits; D011963:Receptors, GABA-A; D001569:Benzodiazepines; C042957:Ro 15-4513