Wong DF, Comley RA, Kuwabara H, Rosenberg P, Resnick SM, Ostrowitzki S, Vozzi C, Boess F, Oh E, Lyketsos CG, Horner M, Gobbi L, Klein G, George N, Gapasin L, Kitzmiller K, Roberts J, Sevigny J, Nandi A, Brasic J, Mishra C, Thambisetty M, Mogekar A, Mathur A, Albert M, Dannals RF, Borroni E. First in-human PET study of 3 novel tau radiopharmaceuticals: [11C]RO6924963, [11C]RO6931643, and [18F]RO6958948. J Nucl Med jnumed.118.209916 published ahead of print May 4, 2018

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Comments

  1. These papers are welcome additions to the literature. The Wong et al. paper exemplifies more recently developed tau radiopharmaceuticals, and the Betthauser et al. paper reaffirms the need for thorough evaluations of newer agents by independent academic centers.  A couple things struck me. First, late-stage, catastrophic tau deposition is now readily detectable with PET as very high signal in the expected neocortices. This is a tremendous success for the field, but for AD prevention trials we need to detect reversal of early-stage tauopathy where weaker signal emerges from medial temporal regions. Kinetic properties need to be carefully demonstrated with focus on serial measures in early stages.

    Second, leptomeningeal off-target binding is evident in tau PET tracers, including in these two reports. We will need autoradiography data as well as postmortem correlations to clarify the exact substrate. These two problems are related: meningeal signal that rises in later frames (see Betthauser et al., Figure 2) could spill into brain and obscure early tau change when serial PET acquisitions fail to measure the same span of the kinetic curve at followup. The new papers move us closer to overcoming these barriers and help clarify the path forward.

    Finally, we deserve better from the Journals. The technology used to report our image data has not changed in decades. Only a tiny fraction of the image data supporting the science is available for reviewers and readers to judge. We need to see entire image data volumes, not the 2 percent sample provided, so we can evaluate entorhinal, substantia nigra, retina, choroid plexus, signal dynamics, etc., etc.

    View all comments by Keith Johnson

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