Classics in Neuroimaging: Development of PET Imaging Agents for Imaging Monoamine Oxidases

In this Viewpoint, we highlight the history of positron emission tomography (PET) imaging agent development to quantify changes in monoamine oxidase (MAO)-A and -B enzyme expression or activity. MAO-A and-B have been central for our understanding of the dopaminergic pathway with applications in neuropsychiatric medicine of high socioeconomic burden, spanning from aging, addictions and mood disorders; as well as, uses in neurodegenerative diseases and disorders with MAO-B expression in astrogliosis, and putative applications in imaging the sympathetic neurons of the peripheral nervous system. This exploration has sparked unique radiochemical innovations including the clinical translation of irreversible propargylamine-based suicide inhibitors, application of deuterium-substitution to slow down metabolism, development of trapped metabolite imaging agents and unique (11)C-carbonylation chemistry to translate novel high-affinity reversibly-binding inhibitors for this important target.