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 Holt, Hiroto Kuwabara, Heather Valentine, Robert F DannalsDean Foster Wong, Edilio Borroni

Research output: Contribution to journalArticle

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

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Positron-Emission Tomography
Amines
Alzheimer Disease
Neurofibrillary Tangles
Amyloid Plaques
Primates
Pharmacokinetics
Biomarkers
Brain
Therapeutics

ASJC Scopus subject areas

  • Molecular Medicine
  • Drug Discovery

Cite this

Identification of Three Novel Radiotracers for Imaging Aggregated Tau in Alzheimer's Disease with Positron Emission Tomography. / Gobbi, Luca C.; Knust, Henner; Körner, Matthias; Honer, Michael; Czech, Christian; Belli, Sara; Muri, Dieter; Edelmann, Martin R.; Hartung, Thomas; Erbsmehl, Isabella; Grall-Ulsemer, Sandra; Koblet, Andreas; Rueher, Marianne; Steiner, Sandra; Ravert, Hayden T.; Mathews, William B; Holt, Daniel; Kuwabara, Hiroto; Valentine, Heather; Dannals, Robert F; Wong, Dean Foster; Borroni, Edilio.

In: Journal of Medicinal Chemistry, Vol. 60, No. 17, 14.09.2017, p. 7350-7370.

Research output: Contribution to journalArticle

Gobbi, LC, Knust, H, Körner, M, Honer, M, Czech, C, Belli, S, Muri, D, Edelmann, MR, Hartung, T, Erbsmehl, I, Grall-Ulsemer, S, Koblet, A, Rueher, M, Steiner, S, Ravert, HT, Mathews, WB, Holt, D, Kuwabara, H, Valentine, H, Dannals, RF, Wong, DF & Borroni, E 2017, 'Identification of Three Novel Radiotracers for Imaging Aggregated Tau in Alzheimer's Disease with Positron Emission Tomography', Journal of Medicinal Chemistry, vol. 60, no. 17, pp. 7350-7370. https://doi.org/10.1021/acs.jmedchem.7b00632
Gobbi, Luca C. ; Knust, Henner ; Körner, Matthias ; Honer, Michael ; Czech, Christian ; Belli, Sara ; Muri, Dieter ; Edelmann, Martin R. ; Hartung, Thomas ; Erbsmehl, Isabella ; Grall-Ulsemer, Sandra ; Koblet, Andreas ; Rueher, Marianne ; Steiner, Sandra ; Ravert, Hayden T. ; Mathews, William B ; Holt, Daniel ; Kuwabara, Hiroto ; Valentine, Heather ; Dannals, Robert F ; Wong, Dean Foster ; Borroni, Edilio. / Identification of Three Novel Radiotracers for Imaging Aggregated Tau in Alzheimer's Disease with Positron Emission Tomography. In: Journal of Medicinal Chemistry. 2017 ; Vol. 60, No. 17. pp. 7350-7370.
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AU - Gobbi, Luca C.

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AU - Körner, Matthias

AU - Honer, Michael

AU - Czech, Christian

AU - Belli, Sara

AU - Muri, Dieter

AU - Edelmann, Martin R.

AU - Hartung, Thomas

AU - Erbsmehl, Isabella

AU - Grall-Ulsemer, Sandra

AU - Koblet, Andreas

AU - Rueher, Marianne

AU - Steiner, Sandra

AU - Ravert, Hayden T.

AU - Mathews, William B

AU - Holt, Daniel

AU - Kuwabara, Hiroto

AU - Valentine, Heather

AU - Dannals, Robert F

AU - Wong, Dean Foster

AU - Borroni, Edilio

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