@article{35049d0acea4419890bbf65b5bf637b6,
title = "Identification of Three Novel Radiotracers for Imaging Aggregated Tau in Alzheimer's Disease with Positron Emission Tomography",
abstract = "Aggregates of tau and beta amyloid (Aβ) plaques constitute the histopathological hallmarks of Alzheimer's disease and are prominent targets for novel therapeutics as well as for biomarkers for diagnostic in vivo imaging. In recent years much attention has been devoted to the discovery and development of new PET tracers to image tau aggregates in the living human brain. Access to a selective PET tracer to image and quantify tau aggregates represents a unique tool to support the development of any novel therapeutic agent targeting pathological forms of tau. The objective of the study described herein was to identify such a novel radiotracer. As a result of this work, we discovered three novel PET tracers (2-(4-[11C]methoxyphenyl)imidazo[1,2-a]pyridin-7-amine 7 ([11C]RO6924963), N-[11C]methyl-2-(3-methylphenyl)imidazo[1,2-a]pyrimidin-7-amine 8 ([11C]RO6931643), and [18F]2-(6-fluoropyridin-3-yl)pyrrolo[2,3-b:4,5-c′]dipyridine 9 ([18F]RO6958948)) with high affinity for tau neurofibrillary tangles, excellent selectivity against Aβ plaques, and appropriate pharmacokinetic and metabolic properties in mice and non-human primates.",
author = "Gobbi, {Luca C.} and Henner Knust and Matthias K{\"o}rner and Michael Honer and Christian Czech and Sara Belli and Dieter Muri and Edelmann, {Martin R.} and Thomas Hartung and Isabella Erbsmehl and Sandra Grall-Ulsemer and Andreas Koblet and Marianne Rueher and Sandra Steiner and Ravert, {Hayden T.} and Mathews, {William B.} and Holt, {Daniel P.} and Hiroto Kuwabara and Heather Valentine and Dannals, {Robert F.} and Wong, {Dean F.} and Edilio Borroni",
note = "Funding Information: We sincerely thank Roland Humm and the scientists at Chembiotek for the synthesis of compounds. We acknowledge the excellent technical assistance in generating the biological data of Patricia Glaentzlin, Ce{\'l} ine Sutter, Svenja Moes, and Jennifer Beck. We thank Christian Bartelmus for collecting HR-MS spectroscopical data and Bjoern Wagner for testing compounds in the LIMBA assay. Additionally we thank the staff of the Johns Hopkins PET Radiotracer Center for their radiochemistry expertise. This study was funded by F. Hoffmann-La Roche Ltd. contract to The Johns Hopkins University (JHU). JHU faculty receive salary support through a number of sponsored research sources including DFW NIH Career Award K24 DA000412, and none receive direct funding from Roche except via sponsored JHU contracts. Publisher Copyright: {\textcopyright} 2017 American Chemical Society.",
year = "2017",
month = sep,
day = "14",
doi = "10.1021/acs.jmedchem.7b00632",
language = "English (US)",
volume = "60",
pages = "7350--7370",
journal = "Journal of medicinal chemistry",
issn = "0022-2623",
publisher = "American Chemical Society",
number = "17",
}