Please use this identifier to cite or link to this item:
Title: Imaging of Reactive Astrogliosis by Positron Emission Tomography.
Austin Authors: Harada, Ryuichi;Furumoto, Shozo;Kudo, Yukitsuka;Yanai, Kazuhiko;Villemagne, Victor L ;Okamura, Nobuyuki
Affiliation: Department of Psychiatry, University of Pittsburgh, Pittsburgh, PA, United States..
Molecular Imaging and Therapy
Department of Pharmacology, Tohoku University Graduate School of Medicine, Sendai, Japan..
Cyclotron and Radioisotope Center, Tohoku University, Sendai, Japan..
Department of New Therapeutics Innovation for Alzheimer's and Dementia, Institute of Development and Aging, Tohoku University, Sendai, Japan..
Division of Pharmacology, Faculty of Medicine, Tohoku Medical and Pharmaceutical University, Sendai, Japan..
Issue Date: 8-Feb-2022 2022
Publication information: Frontiers in neuroscience 2022; 16: 807435
Abstract: Many neurodegenerative diseases are neuropathologically characterized by neuronal loss, gliosis, and the deposition of misfolded proteins such as β-amyloid (Aβ) plaques and tau tangles in Alzheimer's disease (AD). In postmortem AD brains, reactive astrocytes and activated microglia are observed surrounding Aβ plaques and tau tangles. These activated glial cells secrete pro-inflammatory cytokines and reactive oxygen species, which may contribute to neurodegeneration. Therefore, in vivo imaging of glial response by positron emission tomography (PET) combined with Aβ and tau PET would provide new insights to better understand the disease process, as well as aid in the differential diagnosis, and monitoring glial response disease-specific therapeutics. There are two promising targets proposed for imaging reactive astrogliosis: monoamine oxidase-B (MAO-B) and imidazoline2 binding site (I2BS), which are predominantly expressed in the mitochondrial membranes of astrocytes and are upregulated in various neurodegenerative conditions. PET tracers targeting these two MAO-B and I2BS have been evaluated in humans. [18F]THK-5351, which was originally designed to target tau aggregates in AD, showed high affinity for MAO-B and clearly visualized reactive astrocytes in progressive supranuclear palsy (PSP). However, the lack of selectivity of [18F]THK-5351 binding to both MAO-B and tau, severely limits its clinical utility as a biomarker. Recently, [18F]SMBT-1 was developed as a selective and reversible MAO-B PET tracer via compound optimization of [18F]THK-5351. In this review, we summarize the strategy underlying molecular imaging of reactive astrogliosis and clinical studies using MAO-B and I2BS PET tracers.
DOI: 10.3389/fnins.2022.807435
ORCID: 0000-0002-5832-9875
Journal: Frontiers in neuroscience
PubMed URL: 35210989
PubMed URL:
ISSN: 1662-4548
Type: Journal Article
Subjects: MAO-B
imidazoline2 binding site
reactive astrogliosis
Appears in Collections:Journal articles

Show full item record

Page view(s)

checked on May 29, 2023

Google ScholarTM


Items in AHRO are protected by copyright, with all rights reserved, unless otherwise indicated.