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Estimation of Serotonin Transporter Parameters with ¹¹C-DASB in Healthy Humans: Reproducibility and Comparison of Methods

¹ Department of Psychiatry, Columbia University College of Physicians and Surgeons and the New York State Psychiatric Institute, New York, New York; ² Translational Medicine and Genetics, GlaxoSmithKline, Greenford, United Kingdom; and ³ Department of Radiology, Columbia University College of Physicians and Surgeons and the New York State Psychiatric Institute, New York, New York

View larger version (11K): [in a new window]   FIGURE 1.  (A) Mean ± SD of total plasma activity normalized to injected dose [Bq/(mL x MBq ID) after injection of 11C-DASB. Each point is mean of 9 subjects. After a rapid distribution, plasma activity stabilized to a relatively constant level. (B) Mean ± SD of fraction of plasma activity corresponding to parent compound after injection of 11C-DASB. Values are mean of 9 subjects. (C) Mean plasma activity corresponding to parent compound after injection of 11C-DASB. Each point is mean of 9 subjects.

View larger version (21K): [in a new window]   FIGURE 2.  Regional time–activity curves measured after injection of 551.3 MBq 11C-DASB in 33-y-old female. Regions displayed include MID (), STR (), MTL (), MPFC (), and CER (). Points are measured activities in ROIs; lines are fitted values to 1TC model (solid line) and 2TC model (dashed line). Fits for both models are similar.

View larger version (10K): [in a new window]   FIGURE 3.  Relationship between impulse response fraction (IRF) generated from kinetic 2TC data and model order chosen by DEPICT. In the case when the IRF is small (<0.005, below dashed horizontal line), model order is spread between 1TC and 2TC without clear bias toward one or the other. However, for IRF of >0.005, the DEPICT method settled nearly exclusively on the 2TC model. This is particularly evident for IRF of >0.01 (above solid horizontal line).