Fig. 4

Off-target binding of selected first- (left portion of the figure) and second (right portion of the figure) -generation tau PET ligands. Images are taken from amyloid-β-positive Alzheimer’s disease (AD) patients; research clinical diagnosis, age, and mini-mental state examination results are as follows: [¹⁸F]THK5351, prodromal AD, 70, 30; (Karolinska Institutet, Center for Alzheimer Research); [35] [¹¹C]PBB3 prodromal AD, 53, 27 (Karolinska Institutet, Center for Alzheimer Research); [153] [¹⁸F]AV1451, AD dementia, 79, 22 (image courtesy of ADNI); [¹⁸F]RO-948, AD dementia, 66, 22 (image courtesy of Oskar Hansson and the Swedish BioFINDER study); [¹⁸F]MK-6240, AD dementia, 73, 24 and [¹⁸F]PI-2620, AD dementia, 57, 23 (images courtesy of Christopher Rowe and Victor Villemagne). The main areas of known off-target binding for the second-generation tau tracers are marked with circles. The load of this off-target binding across the different tracers is graded in a semiquantitative manner in a table in the lower portion of the figure. Specific non-tau targets for this binding have been reported as briefly named in parentheses and illustrated in detail in Table 1. The wider dynamic range of the second-generation tau tracers can be seen as well as the lower binding in the MAO-B rich basal ganglia (BG) and thalamus (THA). Different scales were used to better illustrate the regional distribution pattern of binding for each tracer, due to between-patient differences as well as due to the different PET acquisition parameters and quantification that were applied for each tracer. Other reported off-target binding areas for the second-generation tau tracers are not presented in this figure [27, 29]. Areas of the cerebellar cortex were used as reference for creating parametric images for all the tracers. CP choroid plexus, DVS dural venous sinuses, SN substantia nigra, BG basal ganglia, DN dentate nucleus, DVR distribution volume ratio, MB midbrain, NFTs neurofibrillary tangles, PMC primary motor cortex, R repeats of the microtubule-binding domain, SUVR standardized uptake value ratio, TL temporal lobe, TP temporal pole, TCX temporal cortex, WM white matter