PET imaging of monoamine oxidase B

Abstract

The monoamine oxidase B (MAO-B) enzyme has a prominent role in brain function, being involved in the breakdown of monoaminergic neurotransmitters. Abnormally high MAO-B levels in the brain, found across different neurological and neurodegenerative disorders including Alzheimer's disease (AD) and Parkinson's disease (PD), are associated with deleterious effects involving reduc tions in dopamine levels and increased oxidative stress, astrocytosis, and neuroinflammation. Recent advances in positron emission tomography (PET) using radiotracers specific to MAO-B have allowed the in vitro and in vivo investigation of the brain regional and temporal patterns of MAO-B in normal aging and brain disorders including depression, AD, PD, and amyotrophic lateral sclerosis (ALS). Multiple MAO-B tracers, characterized by either irreversible or reversible binding kinetics, have been under development and validation over the past ~30 years. Recent multimodal MRI-PET studies have allowed investigating MAO-B in relation to other pathophysiological changes including amyloid-β and tau deposition, glucose metabolism, and brain structural changes. PET imaging of MAO-B is also useful for the monitoring of clinical trials of MAO-B inhibitors. This chapter presents a review of in vivo PET imaging studies of MAO-B from preclinical to clinical applications as well as in vitro autoradiography investigations, highlighting recent progress in the field and future prospects.