Article Figures & Data
Figures
- FIGURE 1.
Chemical structures of 11C-MK-8278, MK-0249, and MK-3134.
- FIGURE 2.
Autoradiography of 11C-MK-8278 imaging in rhesus monkey versus summed image (0–100 min) in human subject. Coronal slices through level of nucleus accumbens and globus pallidus are shown. BST = bed stria terminalis; Cd-Pu = caudate-putamen; CG = cingulate gyrus; GP = globus pallidus; VP = ventropallidal.
- FIGURE 3.
Dynamic human biodistribution of 11C-MK-8278. Maximal-intensity projections at consecutive time intervals (normalized on image maximum).
- FIGURE 4.
Orthogonal sections of summed late-time images (60–80 min) of 11C-MK-8278 in human brain.
- FIGURE 5.
11C-MK-8278 time–activity curves in brain of male, healthy volunteer under baseline condition (A) and after dosing with 2 different doses of MK-0249 (B).
- FIGURE 6.
Transverse images at level of striatum for 3 consecutive healthy volunteers, showing RO changes for MK-0249 with 2.5- and 12.5-mg administration, 6 h postdose. Color scale indicates SUVs.
- FIGURE 7.
(A) Occupancy versus dose relationship for MK-0249 (▲) and MK-3134 (▪) and fitted Hill curves. (B) Occupancy versus plasma concentration relationship for MK-0249 (▲, 6 h postdose; △, 27 h postdose) and for MK-3134 (▪, 6 h postdose).
Tables
Target organ Mean (μGy/MBq) Mean (mGy/300 MBq) Variance (%) Pancreas 40.2 12.1 32.3 Small intestine 16.4 4.91 2.3 Lungs 14.4 4.33 31.4 Liver 14.4 4.32 16.0 Kidneys 13.6 4.08 22.4 Spleen 11.1 3.33 51.6 Thyroid 6.2 1.87 26.7 Urinary bladder wall 5.0 1.49 9.7 Gallbladder wall 4.8 1.44 30.5 Heart wall 4.5 1.36 32.0 Brain 3.9 1.16 6.9 Upper large intestine wall 3.4 1.02 4.6 Adrenals 3.0 0.91 12.5 Ovaries 2.4 0.73 6.6 Stomach wall 2.4 0.73 12.6 Uterus 2.4 0.71 7.4 Total body (remainder) 2.3 0.70 10.0 Osteogenic cells 2.1 0.63 18.9 Red marrow 2.1 0.63 20.2 Lower large intestine wall 2.0 0.59 8.6 Thymus 1.6 0.47 11.4 Muscle 1.5 0.44 10.9 Breasts 1.4 0.41 11.5 Skin 1.0 0.30 12.7 Testes 1.0 0.30 16.0 Effective dose 5.4 (μSv/MBq) 1.63 (mSv/300 MBq) 19.8 11C-MK-8278 VT BPND Organ Mean SD Mean SD Striatum 17.1 1.9 2.16 0.07 Thalamus 8.8 0.9 0.86 0.08 Mid brain 9.8 1.2 1.00 0.09 Frontal 8.4 0.7 0.81 0.13 Anterior cingulate gyrus 10.2 1.1 1.15 0.21 Posterior cingulate gyrus 8.9 1.1 0.92 0.26 Parietal 7.9 0.8 0.69 0.08 Insula 8.6 0.8 0.84 0.12 Temporal 7.7 0.7 0.66 0.09 Occipital 7.0 0.5 0.53 0.08 Cerebellum 7.4 0.5 0.64 0.13 Pons 4.5 0.5 White matter 3.7 0.4 Subject no. Activity (MBq) Dose (mg) H3 RO (%, striatum) Plasma level (nM) Time scan (h postdose) MK-0249 Panel A 1 273 Baseline — — — 2 234 Baseline — — — 3 259 Baseline — — — 1 296 2.5 60 3.9 6 2 275 2.5 61 4.0 6 3 261 2.5 63 0.9 6 1 273 12.5 88 19.5 6 2 265 12.5 87 24.3 6 3 282 12.5 90 16.9 6 Panel B 4 298 Baseline — — — 5 282 Baseline — — — 6 265 Baseline — — — 4 286 7.5 80 8.5 6 5 288 7.5 80 12.4 6 6 256 7.5 77 7.8 6 4 269 50 94 97.9 6 5 274 50 93 99.4 6 6 267 50 93 89.7 6 Panel E 13 259 Baseline — — — 14 280 Baseline — — — 15 278 Baseline — — — 13 264 10 87 23.3 6 14 275 10 88 13.8 6 15 277 10 89 18.5 6 13 261 10 73 7.4 27 14 284 10 69 4.0 27 15 256 10 69 5.7 27 MK-3134 Panel A 1 267 Baseline — — — 2 274 Baseline — — — 3 309 Baseline — — — 1 292 1 69 0.8 6 2 304 1 66 0.7 6 3 296 1 67 0.6 6 1 273 5 89 4.3 6 2 273 5 92 4.6 6 3 296 5 88 2.5 6 Panel B 4 285 Baseline — — — 5 293 Baseline — — — 6 302 Baseline — — — 4 289 0.5 47 BLQ 6 5 264 0.5 46 BLQ 6 6 256 0.5 43 BLQ 6 4 283 25 94 6.9 6 5 263 25 97 11.8 6 6 306 25 96 11.0 6 BLQ = below level of quantification.
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