No in vivo imaging biomarker currently exists for BACE, a drug target for Alzheimer's disease (AD). A strategy aiming to find a novel brain-penetrant positron emission tomography (PET) radiotracer for BACE1 led to the discovery of a highly potent and selective aminothiazine inhibitor, PF-06684511. This scaffold has been now evaluated as BACE1 PET radiotracer ([18F]PF-06684511) after labeling with fluorine-18 (18F), allowing its evaluation in non-human primates (NHP) as the first a brain-penetrant PET radiotracer for imaging BACE1 in vivo.