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

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.