Fig. 5.

Representation of a tau protofibril, showing four high-affinity binding sites (core sites: 1, 3, and 4; surface site, 2) for tau PET ligands, as determined via in silico modeling. With the exception of [¹⁸F]T808, all the studied tracers ([¹⁸F]AV1451, [¹⁸F]FDDNP, [¹¹C]PBB3, [¹⁸F]THK5105, [¹⁸F]THK523, [¹⁸F]THK5351, [¹⁸F]THK5117, [¹⁸F]MK-6240, [¹⁸F]RO-948, and [¹⁸F]JNJ311) have shown significant binding to these four sites. On the basis of molecular docking scores, however, tracers such as [¹⁸F]FDDNP, [¹⁸F]THK5351, [¹⁸F]RO6955, and [¹⁸F]MK-6240 bind preferentially to the core sites, while [¹¹C]PBB3 and [¹⁸F]THK523 bind preferentially to site 2. Certain ligands, moreover, such as [¹⁸F]THK5317 and [¹⁸F]JNJ311, show similar binding affinities to several sites. Adapted with permission from American Chemical Society Publications, Murugan et al. [151]. (ACS Chem Neurosci. 2018. Copyright 2018)