Identification of Three Novel Radiotracers for Imaging Aggregated Tau in Alzheimer's Disease with Positron Emission Tomography

Luca C. Gobbi, Henner Knust, Matthias Körner, Michael Honer, Christian Czech, Sara Belli, Dieter Muri, Martin R. Edelmann, Thomas Hartung, Isabella Erbsmehl, Sandra Grall-Ulsemer, Andreas Koblet, Marianne Rueher, Sandra Steiner, Hayden T. Ravert, William B. Mathews, Daniel P. Holt, Hiroto Kuwabara, Heather Valentine, Robert F. DannalsDean F. Wong, Edilio Borroni

Research output: Contribution to journalArticlepeer-review

40 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)7350-7370
Number of pages21
JournalJournal of medicinal chemistry
Volume60
Issue number17
DOIs
StatePublished - Sep 14 2017

ASJC Scopus subject areas

  • Molecular Medicine
  • Drug Discovery

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