A Novel (18)F-Labeled Imidazo[2,1-b]benzothiazole (IBT) for High-Contrast PET Imaging of β-Amyloid Plaques

Behrooz H Yousefi; Alexander Drzezga; Boris von Reutern; André Manook; Markus Schwaiger; Hans-Jürgen Wester; Gjermund Henriksen

doi:10.1021/ml200123w

A Novel (18)F-Labeled Imidazo[2,1-b]benzothiazole (IBT) for High-Contrast PET Imaging of β-Amyloid Plaques

ACS Med Chem Lett. 2011 Jul 19;2(9):673-7. doi: 10.1021/ml200123w. eCollection 2011 Sep 8.

Authors

Behrooz H Yousefi¹, Alexander Drzezga¹, Boris von Reutern¹, André Manook¹, Markus Schwaiger¹, Hans-Jürgen Wester², Gjermund Henriksen¹

Affiliations

¹ Department of Nuclear Medicine, Klinikum rechts der Isar, Technische Universität München , Ismaninger Strasse 22, 81675 München, Germany.
² Lehrstuhl für Pharmazeutische Radiochemie , Walther-Meissner-Strasse 3, 85748 Garching, Germany.

Abstract

(18)F-labeled imidazo[2,1-b]benzothiazole ([(18)F]8) was synthesized and evaluated as a tracer for cerebral β-amyloid deposits (Aβ) by means of positron emission tomography (PET). [(18)F]8 exhibits a high affinity to Aβ and suitable brain uptake kinetics combined with a high metabolic stability in the brain. In a double transgenic APP/PS1 mouse model of Alzheimer's disease, we demonstrated a specific uptake of [(18)F]8 in Aβ-containing telencephalic brain regions. The specific binding of [(18)F]8 to Aβ was confirmed by regional brain biodistribution and autoradiography and correlated to immunohistochemistry staining. Analysis of brain sections of APP/PS1 mouse injected with a cocktail of [(18)F]8 and reference compound [(3)H]PiB revealed that the two tracers bind to Aβ plaques in the brain of mouse in a comparable binding pattern. [(18)F]8 represents the first high-contrast PET imaging agent for detection of Aβ plaques in transgenic mouse model of Alzheimer's disease and holds promise for transfer to a clinical evaluation.

Keywords: 18F-labeled tracer for β-amyloid; APP/PS1transgenic mice; Alzheimer's disease; IBT; autoradiography; neuroimaging; positron emission tomography; β-amyloid plaques.