Article Figures & Data
Figures
- FIGURE 1.
Representative PET images after 11C-GSK189254 administration to a healthy human subject before (top) and 4 h after (middle) a 50-μg oral dose of GSK189254. Mean standardized uptake value images over 0–90 min are shown with structural MR image for same subject (bottom).
- FIGURE 2.
Typical time–activity curves from 1 subject and corresponding plasma input functions after intravenous administration of 11C-GSK189254 at baseline (A) and 4 h after 100 μg of GSK189254 (B), together with corresponding best fits. SUV = standardized uptake value.
- FIGURE 3.
Assessment of stability of VT estimates from differing baseline scan durations for cerebellum (A), frontal cortex (B), and putamen (C). Data are presented as mean percentage (±SD) of value obtained using full 90-min dataset.
- FIGURE 4.
Graphical estimation of occupancy and VND of GSK189254. Occupancy is given by slope and VND by intercept with x-axis. Each data point represents difference in VT for single ROI for individual subjects before and 4 h after GSK189254 administration at 100-μg (n = 1) (A), 50-μg (n = 3) (B), 25-μg (n = 2) (C), and 10-μg (n = 3) (D) doses.
- FIGURE 5.
Dose–occupancy relationship of orally administered GSK189254 (4 h after dosing), together with least-squares fit of Equation 2 to data.
- FIGURE 6.
Typical fits to representative occipital time–activity curves from 1 subject after intravenous administration of 11C-GSK189254. Standardized uptake values are shown from test (○) and retest (▵) scans illustrating carryover effect. SUV = standardized uptake value.
Tables
ROI Test (mean ± SD) Retest (mean ± SD) Caudate 96.7 ± 31.2 61.9 ± 27.6 Putamen 119 ± 21.7 68.4 ± 8.9* Cerebellum 22.5 ± 4.5 17.6 ± 2.7* Frontal cortex 32.0 ± 3.4 23.3 ± 1.9† Parietal cortex 26.8 ± 3.1 20.5 ± 1.6† Occipital cortex 23.9 ± 3.6 18.5 ± 2.0* Insular cortex 47.4 ± 12.4 30.4 ± 2.6‡ Anterior cingulate cortex 50.2 ± 13.3 50.2 ± 13.3‡ Hippocampus 26.3 ± 4.0 20.7 ± 4.6† Amygdala 42.3 ± 3.4 30.0 ± 5.3* Thalamus 24.5 ± 1.8 19.8 ± 2.1* 4 h after administration of… ROI Baseline (n = 15) 100 μg (n = 1) 50 μg (n = 3) 25 μg (n = 2) 10 μg (n = 3) 24 h after administration of 25 μg (n = 6) Caudate 69.9 ± 26.9* 15.0 15.8 ± 3.2 16.1 24.8 ± 4.2 30.7 ± 18.7* Putamen 95.2 ± 7.8 17.3 22.2* 25.7 31.5 ± 5.3 44.6 ± 18.5 Cerebellum 22.2 ± 3.5 8.50 10.5 ± 0.8 10.5 14.2 ± 1.8 14.5 ± 2.5 Frontal cortex 28.4 ± 4.2 9.95 12.3 ± 0.9 12.1 16.2 ± 2.9 17.9 ± 3.5 Parietal cortex 24.2 ± 3.7 9.53 11.6 ± 0.5 10.8 14.6 ± 2.3 16.3 ± 3.2 Occipital cortex 21.8 ± 3.2 9.12 11.4 ± 0.8 10.5 13.5 ± 1.7 15.4 ± 2.2 Insula cortex 38.7 ± 7.1 12.6 14.8 ± 1.4 16 19.2 ± 3.1 23.5 ± 4.0 Anterior cingulate cortex 44.8 ± 14.6 12.6 14.5 ± 1.4 16.4 21.0 ± 4.0 23.3 ± 4.6 Hippocampus 22.8 ± 3.6 9.25 10.1 ± 0.8 10 13.4 ± 1.5 15.0 ± 2.7 Amygdala 36.5 ± 10.6 10.9 12.1 ± 0.5 14.9 17.5 ± 3.9 20.6 ± 5.3 Thalamus 23.5 ± 3.4 10.7 11.2 ± 0.9 10.7 15.0 ± 2.2 16.5 ± 3.7 ↵* Caudate or putamen could not be fitted for 1 subject.
Bmax (nM) Subject no. koff (min−1) KD (nM) Cerebellum Occipital cortex Putamen 1 0.015 0.0131 0.74 0.95 5.1 2 0.021 0.0093 0.75 0.69 4.1 3 0.031 0.0064 0.48 0.62 2.9 4 0.029 0.0094 0.66 0.75 3.6 5 0.020 0.0093 0.33 0.50 3.1 Mean 0.023 0.0095 0.59 0.70 3.8 SD 0.007 0.0024 0.18 0.17 0.9
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