Tau PET Imaging

Abstract

The deposition of fibrillar tau aggregates has been implicated in Alzheimer’s disease (AD) and allied neurodegenerative disorders collectively referred to as tauopathies. Growing non-clinical and clinical evidence has supported intimate links between tau fibrillogenesis and neuronal deteriorations, rationalizing the development of imaging agents for tau fibrils to gain etiological insights into tauopathies and to facilitate diagnostic and therapeutic approaches to these diseases. Radiochemicals derived from three major chemotypes were initially applied to positron emission tomography (PET) studies of human subjects, demonstrating their utility for capturing AD-type tau deposits with reasonably high contrast. Meanwhile, these tracers suffered substantial off-target binding in the brain and did not offer sensitive detection of tau lesions in a large proportion of non-AD tauopathies. To overcome such drawbacks, ‘second-generation’ tau PET probes have been generated and examined in clinical settings. These tracers have enabled specific assays of AD tau pathologies, and a novel radiocompound developed by our research group has been shown to produce high contrasts for AD and non-AD tau aggregates, potentially allowing diagnostic evaluations of diverse tauopathies on an individual basis.