Quantitative analysis for estimating binding potential of the brain serotonin transporter with [11 C]McN5652.
[11C](+)McN5652 is a selective serotonin reuptake inhibitor with subnanomolar potency for the serotonin transporter, and is currently being used for positron emission tomography studies. However, quantification of the regional [11C](+)McN5652 binding potential in vivo is a controversial issue because of its complex characteristics. The authors examined the regional differences in nonspecific binding and proposed simple methods for estimating the binding potential of [11C](+)McN5652. The regional difference in nonspecific binding was evaluated by the activity ratio of the thalamus compared with the cerebellum for inactive-isomer [11C](-)McN5652 and [11C](+)McN5652 saturation studies. The distribution volume of the thalamus was approximately 1.16 times larger than that of the cerebellum. The thalamus-to-cerebellum distribution volume ratio was estimated by nonlinear least square and graphical methods, with and without arterial input function. The graphical method with k2; without blood sampling was practical and most applicable for estimation of the distribution volume ratio because this method is more stable than the nonlinear least square method in the simulation study. Binding potential estimated with the distribution volume ratio of [11C](+)McN5652 and the correction with distribution volume ratio of [11C](-)McN5652 represent the most reliable parameters for the assessment of serotonin transporter binding.
Ikoma
Yoko
Y
Department of Science and Engineering, Waseda University, Tokyo, Japan.
Suhara
Tetsuya
T
Toyama
Hinako
H
Ichimiya
Tetsuya
T
Takano
Akihiro
A
Sudo
Yasuhiko
Y
Inoue
Makoto
M
Yasuno
Fumihiko
F
Suzuki
Kazutoshi
K
D000328:Adult; D001921:Brain / Q000187:drug effects / Q000378:metabolism*; D002250:Carbon Radioisotopes / Q000097:blood / Q000378:metabolism; D002352:Carrier Proteins / Q000378:metabolism*; D006801:Humans; D007546:Isoquinolines / Q000097:blood / Q000378:metabolism*; D008297:Male; D008433:Mathematics; D008562:Membrane Glycoproteins / Q000378:metabolism*; D026901:Membrane Transport Proteins; D008875:Middle Aged; D009419:Nerve Tissue Proteins / Q000378:metabolism; D011485:Protein Binding; D012044:Regression Analysis; D012702:Serotonin Antagonists / Q000097:blood / Q000378:metabolism; D050486:Serotonin Plasma Membrane Transport Proteins; D017367:Selective Serotonin Reuptake Inhibitors / Q000494:pharmacology; D013997:Time Factors; D014055:Tomography, Emission-Computed
D002250:Carbon Radioisotopes; D002352:Carrier Proteins; D007546:Isoquinolines; D008562:Membrane Glycoproteins; D026901:Membrane Transport Proteins; D009419:Nerve Tissue Proteins; D012702:Serotonin Antagonists; D050486:Serotonin Plasma Membrane Transport Proteins; D017367:Selective Serotonin Reuptake Inhibitors; C493230:SLC6A4 protein, human; C058079:McN 5652