PET tracer SMBT‐1 discriminates between BU99008 and Deprenyl binding sites on reactive astrocytes in Alzheimer's disease brains

Astrocytes are the homeostatic cells of the mammalian brain. We recently proposed a “two‐wave” hypothetical model in which reactive astrocytes (RA) are early‐responders to Alzheimer’s disease (AD) pathology and may support a perpetual brain inflammatory state1. Advances in positron emission tomography (PET) imaging biomarkers allow for detecting RA in the early stages of AD (e.g., [11C]‐L‐Deprenyl and [11C]BU99008, which target MAO‐B and the imidazole binding sites 2 – I2Bs, respectively). However, RA assume multiple states, thus, a very heterogenous population of RA exist. Based on a recent consensus, the development of novel PET‐tracers targeting different RA populations is a priority in the field. [18F]‐SMBT‐1, a selective MAO‐B PET‐tracer, was recently designed as an alternative to detect RA in the human brain. However, further studies using [18F]‐SMBT‐1 are needed to evaluate its sensitivity to image RA in AD. We aimed at evaluating the binding properties of SMBT‐1 versus two PET‐tracers targeting RA ‐ [3H]‐L‐Deprenyl and [3H]‐BU99008 ‐ using in vitro human brain techniques.