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Table 2 Characteristics of published tau protein tracers updated from (Villemagne et al. 2015)

From: New protein deposition tracers in the pipeline

Tracer name Chemical structure Features
Pyridinyl-butadienyl-benzothiazole derivative
 [11C]-PBB3 (Maruyama et al. 2013; Hashimoto et al. 2014) • 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
 [18F]-T807 (Chien et al. 2013; Xia et al. 2013) • 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
  1. AD alzheimer’s disease