, 2013 and Okamura et al., 2013) and the Siemens/Lilly group have reported the 18F-labeled T807 and T808 compounds (Chien et al., 2013a and Chien et al., 2013b). Both groups have focused initially upon the binding of their tau-selective radioligands in AD brain, and little information regarding binding properties of these radioligands to the non-AD tauopathies has been reported to date. In this issue of Neuron, Maruyama et al. (2013) describe the in vitro and in vivo properties of a new class of selective tau-binding ligands they term PBBs. Some MG132 of the PBB ligands fluoresce and were used in in vitro assays and in vivo optical imaging studies in a transgenic tauopathy mouse model, while

the most promising PBB ligand (termed PBB3) was radiolabeled with 11C and used in PET imaging studies in the tauopathy mouse model and in elderly cognitively normal, AD, and CBD subjects (a four-repeat predominant tauopathy). There are advantages and disadvantages with the choice of 11C versus 18F radiolabels. The longer half-life of 18F (109.8 min) permits

the regional distribution of the radiopharmaceutical from a central nuclear pharmacy production center and provides generally more convenient PET imaging logistics relative to the shorter half-life 11C (20.4 min) radionuclide. However for research imaging purposes, the 11C radiolabel permits two or more serial PET studies to be conducted in the oxyclozanide same subject

with different radiopharmaceuticals on the same day several hours apart. signaling pathway Maruyama et al. (2013) screened a number of fluorescent compounds for selective binding of the ligands to tau deposits (from both AD and non-AD tauopathies) over Aβ plaques. They found that compounds with extended conjugated backbones with a core length of 15–18 Å bound most favorably to tau. The conjugated butadiene linkage between the two aromatic ring systems of PBBs apparently provides the basis for their high tau binding affinities. It is interesting to note the structural similarities between PiB and PBB3 (Figure 1), yet their binding affinities to aggregated Aβ and tau are very different. Just as surprising is the difference in selectivity between PBB1 (which also binds Aβ plaques) and PBB3 (Figure 1) on tissue sections—although large differences in lipophilicity may account for this. In vitro and ex vivo fluorescence imaging of tau inclusions with PBBs utilized PS19 transgenic mice expressing a FTDP-17 four-repeat tau isoform with the P301S mutation, and tau deposits were apparent in the brain stem and spinal cord of these mice. Other fluorescence imaging experiments were conducted in a second mouse model of tauopathy (rTg4510 mice expressing the FTDP-17 four-repeat P301L mutation), and these mice demonstrated specific binding of PBBs to neuronal tau inclusions in the neocortex and hippocampus.