Journal of Nuclear Medicine, published on September 28, 2017 as doi:10.2967/jnumed.117.196741 Preclinical Evaluation of 18F-RO6958948, 11C-RO6931643 and 11C-RO6924963 as Novel Radiotracers for Imaging Aggregated Tau in Alzheimer’s Disease with Positron Emission Tomography Michael Honer1, Luca Gobbi1, Henner Knust1, Hiroto Kuwabara2,3, Dieter Muri1, Matthias Koerner1, Heather Valentine2,3, Robert F. Dannals2, Dean F. Wong2,3,4,5,6, Edilio Borroni1 1Roche Pharma Research & Early Development, Roche Innovation Center Basel, F. Hoffmann-La Roche Ltd., Basel, Switzerland 2Russell H. Morgan Department of Radiology, Division of Nuclear Medicine – PET Center, The Johns Hopkins University School of Medicine, Baltimore 3Section of High Resolution Brain PET, Division of Nuclear Medicine, The Johns Hopkins University School of Medicine, Baltimore 4Solomon H. Snyder Department of Neuroscience, The Johns Hopkins University School of Medicine, Baltimore 5Department of Psychiatry and Behavioral Sciences, The Johns Hopkins University School of Medicine, Baltimore 6Department of Neurology, The Johns Hopkins University School of Medicine, Baltimore Corresponding author: Dr. Michael Honer Pharma Research and Early Development (pRED) Roche Innovation Center Basel F. Hoffmann-La Roche Ltd. 4070 Basel, Switzerland E-mail:
[email protected] Running foot line: PET imaging of tau Abstract Tau aggregates and amyloid-beta (Aβ) plaques are key histopathological features in Alzheimer‘s disease (AD) and are considered as targets for therapeutic intervention as well as biomarkers for diagnostic in vivo imaging agents. This study describes the preclinical in vitro and in vivo characterization of the 3 novel compounds RO6958948, RO6931643 and RO6924963 that bind specifically to tau aggregates and have the potential to become positron emission tomography (PET) tracers for future human use.