Article Figures & Data
Figures
- FIGURE 1.
Competition assay with 3H-PK11195 and unlabeled PBR28, using tissue from donors with no history of neurologic disease. Each data point represents mean value of all subjects, and error bars represent SEM. Conc = concentration.
- FIGURE 2.
Competition assays with 3H-PK11195 and unlabeled TSPO ligand using brain tissue previously characterized as HAB, LAB, or MAB by PBR28 assays. Each data point represents mean value of at least 4 subjects, and error bars represent SEM. (A) Phenoxyphenyl acetamide derivatives. (B) Bicyclic linker derivatives. (C) Phenyl–isoquinolinecarboxamide derivatives. Conc = concentration; SB = specific binding.
- FIGURE 3.
Competition assays with 3H-PK11195 and unlabeled PBR111 in presence or absence of PBR28 (50 nM).
- FIGURE 4.
11C- PBR28 PET data from 32 healthy volunteers expressed as histogram with mixture model analysis showing 2 distributions for each measurement. (A) Volume of distribution. (B) Plasma free fraction. (C) Volume of distribution/plasma free fraction. Blue curves denote single-component solutions, and green and black curves denote 2-component solutions. For 2-component solutions, whereas different individuals are within each gaussian group (e.g., green) for 3 parameters, there was good agreement between A and B (74%) and A and C (66%).
- FIGURE 5.
TSPO ligands displayed in structural classes.
Tables
- TABLE 1
Competition Binding Studies with PK11195, PBR28, PBR06, PBR111, DPA713, and DAA1106
Ki (nM) of… Binding class PK11195* PBR28* PBR06 DPA713 DAA1106 PBR111 HABs 28.3 ± 4.0 (n = 6) 3.4 ± 0.2 (n = 6) 8.6 ± 2.0 (n = 5) 15.0 ± 2.2 (n = 5) 2.8 ± 0.3 (n = 4) 15.6 ± 3.7 (n = 5) LABs 22.3 ± 2.2 (n = 5) 188 ± 7.0 (n = 5) 149 ± 46.6 (n = 4) 66.4 ± 7.8 (n = 4) 13.1 ± 1.3 (n = 4) 61.8 ± 10.7 (n = 5) MABs 23.6 ± 5.5 (n = 4) Two receptors detected (n = 4): 4.0 ± 1.2 (high) and 313 ± 38 (low) Two receptors detected (n = 4): 13.4 ± 3.4 (high) and 176 ± 103 (low) 26.8 ± 2.9 (n = 4) 4.8 ± 0.4 (n = 4) 30.3 ± 4.1 (n = 4) Ki ratio of LAB to HAB 0.8 55 17 4.4 4.7 4.0 t test HAB vs. LAB P < 0.25 P < 0.0001 P < 0.011 P < 0.001 P < 0.001 P < 0.003 MAB vs. LAB P < 0.82 NA NA P < 0.003 P < 0.001 P < 0.04 MAB vs. HAB P < 0.50 NA NA P < 0.01 P < 0.005 P < 0.03 ↵* Data reproduced from Owen et al. (6).
NA = not applicable.
Data are expressed as mean ± SEM. All data in Table 1 were generated from donors B1–B15, inclusive.
Ki (nM) of… Reduction (%) in specific signal after block with PBR28 (50 nM) Binding class PBR111 PBR111 after block with PBR28 (50 nM) HABs 15.6 ± 3.7 (n = 5) Not measurable 69.0 ± 4.6 (n = 4) LABs 61.8 ± 10.7 (n = 5) 51.7 ± 12.2 (n = 4) 21.2 ± 4.8 (n = 4) MABs 30.3 ± 4.1 (n = 4) 54.4 ± 5.3 (n = 4) 49.3 ± 2.9 (n = 4) t test HAB vs LAB P < 0.003 NA P < 0.0004 MAB vs LAB P < 0.04 P < 0.84 P < 0.002 MAB vs HAB P < 0.03 NA P < 0.01 NA = not applicable.
Data are expressed as mean ± SEM.
Ligand LAB MAB HAB PBR28 1 28.2 55.3 PBR06 1 9.2 17.3 DAA1106 1 2.9 4.7 PBR111 1 2.5 4.0 DPA173 1 2.7 4.4 PK11195 1 0.9 0.8 MABs are assumed to express equal number of HAB and MAB sites. Receptor density is assumed to remain constant. Values are calculated as BPND relative to BPND of LABs.
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