Alzheimer's disease is a devastating, progressive neurodegenerative disease
that is the primary cause of dementia. Its pathology is characterized by the
accumulation of amyloid and tau, and the role of brain inflammation is
increasingly understood as a key mediator of these effects. The specific
neuroinflammation mechanisms implicated in Alzheimer's disease, however, remain
unclear.
Colony stimulating factor 1 receptor (CSF1R) is expressed
exclusively in the brain in microglia and is robustly upregulated in the
post-mortem Alzheimer's disease brain. This provides a compelling imaging
target for human studies of microglia-specific
inflammation.
"While there is considerable interest in developing
CSF1R-targeted PET radiotracers, limited specific binding makes it challenging," noted Hillmer. "Developing a radiotracer with higher specific binding to CSF1R
is a potential game changer to advance the field s understanding of
inflammation in the onset and progression of this devastating disease."
Hillmer and Webb aim to establish 18F-PLX5622 as a next-generation
PET radiotracer suitable for translation to human imaging studies of CSF1R in
people with Alzheimer's disease and related dementias. They will first evaluate
18F-PLX5622 imaging properties and specific binding in a mouse model and will
then confirm cellular specificity. The specific binding of 18F-PLX5622 will
then be assessed in post-mortem tissue from individuals with Alzheimer's
disease.
"This grant will provide a launch platform for use of 18F-PLX5622
as a CSF1R PET radiotracer to diagnose, monitor, and guide treatment for
inflammation in the context of Alzheimer's disease," said Webb. "Our hope is
that this research will directly support future translation to clinical studies
studying brain inflammation in people with Alzheimer's disease."
Hillmer's research leverages pharmacologically specific imaging modalities to study brain mechanisms of neurological and neuropsychiatric conditions. He received his PhD from University of Wisconsin, Madison. Webb's work focuses on developing robust (radio)chemical methodologies that open radiochemical space and readily translate across institutes. He earned his PhD from Princeton University in Princeton, New Jersey.
Established in 2023, the SNMMI Mars Shot Research Fund is a forward-looking glimpse into the future of nuclear medicine. It provides resources that translate visionary nuclear medicine imaging, radiopharmaceutical therapy, and data science research or projects into tools or treatments that will help improve the lives of patients.
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