Table 2 Characteristics of published tau protein tracers updated from (Villemagne et al. 2015)
Tracer name | Chemical structure | Features |
|---|---|---|
Pyridinyl-butadienyl-benzothiazole derivative | ||
| • Selectively binds to tau | |
• Retention of 11C-PBB3 in the venous sinuses | ||
• Retention of tracer in basal ganglia in patient with corticobasal degeneration suggests that it might bind to non-AD tauopathies | ||
Dialkylamino-naphthylethylidene derivative | ||
 [18F] FDDNP (Kepe et al. 2013; Thompson et al. 2009; Small et al. 2013; Shoghi-Jadid et al. 2002; Smid et al. 2013) |
| • First 18F-tracer with tau binding |
• Lack of selectivity for tau; nanomolar binding affinity to Aβ | ||
• Very limited dynamic range | ||
• Regional brain retention used for differentiating Aβ and tau | ||
Benzimidazole derivatives | ||
 [11C]-N-Methyl-Lansoprazole (Shao et al. 2012; Fawaz et al. 2014) |
| • In vitro binding to paired helical filament-tau demonstrated |
• No brain uptake in mice (P-glycoprotein substrate) | ||
• Brain uptake in non-human primates | ||
• No human studies reported | ||
 [18F]-N-Methyl-Lansoprazole (Fawaz et al. 2014) |
| |
Quinoline derivatives | ||
 [18F]-THK-523 (Harada et al. 2013) |
| • Slow kinetics |
• Non-specific binding (white matter, brain stem) | ||
• No detection of non-AD tauopathies (Pick’s disease; three-repeat tauopathy) | ||
 [18F]-THK-5105 (Okamura et al. 2013; Okamura et al. 2014) |
| • Faster kinetics and higher contrast than 18F-THK-523 |
• Non-specific binding (white matter, brain stem) | ||
 [18F]-THK-5117 (Okamura et al. 2013; Okamura et al. 2015) |
| |
 [18F]-THK-5351 (Harada et al. 2015) |
| • Faster kinetics and higher contrast than THK-523 |
• Lower white matter retention | ||
• Higher signal-to-noise ratio compared with 18F-THK-5105 and 18F-THK-5117 | ||
6,5,6 Tricyclic pyrimidines and indoles | ||
| • Tracer with broadest clinical data package | |
• Cortical retention consistent with the known distribution of tau in AD brain | ||
• Strong correlation with disease severity | ||
• Slower kinetics than 18F-T808 | ||
• Off-target activity (striatum, choroid plexus) | ||
 [18F]-T808 (Chien et al. 2014) |
| • Faster kinetics than 18F-T807 |
• Substantial defluorination | ||
Pyrrolo-pyridine-isoquinolineamine | ||
 [18F]-MK-6240 (Walji et al. 2016) |
| • Good in vitro binding affinity to NFTs, high selectivity to β-amyloid, and excellent physicochemical properties for brain penetration and cellular permeability. |
• No off-target binding and suitable in vivo pharmacokinetics | ||
• Clinical studies are currently underway | ||
