Characterization and First Human Investigation of FIBT, a Novel Fluorinated Aβ Plaque Neuroimaging PET Radioligand

Imidazo[2,1-b]benzothiazoles (IBTs) are a promising novel class of amyloid positron emission tomography (PET) radiopharmaceuticals for diagnosis of neurodegenerative disorders like Alzheimer’s disease (AD). Their good in vivo imaging properties have previously been shown in preclinical studies. Among IBTs, fluorinated [18F]FIBT was selected for further characterization and advancement toward use in humans. [18F]FIBT characteristics were analyzed in relation to Pittsburgh compound B (PiB) as reference ligand. [18F]FIBT and [3H]PiB were coinjected to an APP/PS1 mouse for ex vivo dual-label autoradiographic correlation. Acute dose toxicity of FIBT was examined in two groups of healthy mice. Preexisting in vivo stability and biodistribution studies in mice were complemented with analogous studies in rats. [18F]FIBT was titrated against postmortem human AD brain homogenate in a saturation binding assay previously performed with [3H]PiB. Binding of [18F]FIBT to human AD brain was further analyzed by in vitro in...