Anton Lindberg, Junchao Tong, Chao Zheng, Andre Mueller, Heiko Kroth, Andrew Stephens, Chester A Mathis, Neil Vasdev
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引用次数: 0
Abstract
[18F]PI-2620 is a promising radiopharmaceutical for positron emission tomography (PET) imaging of both Alzheimer's disease (AD) and non-Alzheimer's disease (non-AD) tauopathies in humans. An array of fluorinated derivatives of the carbazole scaffold of PI-2620 were synthesized and evaluated. In vitro binding assays with [3H]PI-2620 in human tissues with AD, progressive supranuclear palsy, and corticobasal degeneration, combined with in silico predictions of blood-brain barrier permeability, led to the selection and radiosynthesis of [18F]F-4 as a promising radiotracer. In vivo PET imaging with [18F]F-4 in healthy rats showed brain uptake and kinetics suitable for neuroimaging, similar to those of [18F]PI-2620. A first-in-human PET imaging study in a healthy subject as well as a patient with AD, in comparison with [18F]PI-2620 in the same AD subject, confirmed that [18F]F-4 is an alternative radiopharmaceutical for imaging tau protein.
期刊介绍:
ACS Chemical Neuroscience publishes high-quality research articles and reviews that showcase chemical, quantitative biological, biophysical and bioengineering approaches to the understanding of the nervous system and to the development of new treatments for neurological disorders. Research in the journal focuses on aspects of chemical neurobiology and bio-neurochemistry such as the following:
Neurotransmitters and receptors
Neuropharmaceuticals and therapeutics
Neural development—Plasticity, and degeneration
Chemical, physical, and computational methods in neuroscience
Neuronal diseases—basis, detection, and treatment
Mechanism of aging, learning, memory and behavior
Pain and sensory processing
Neurotoxins
Neuroscience-inspired bioengineering
Development of methods in chemical neurobiology
Neuroimaging agents and technologies
Animal models for central nervous system diseases
Behavioral research