Innovative PET Tracers Enhance Imaging of the Central Nervous System
New PET tracers with longer half-lives advance brain imaging capabilities by targeting the histamine H3 receptor, enhancing diagnosis and research of neurological disorders.
Recent developments in positron emission tomography (PET) imaging have led to the creation of novel tracers targeting the histamine H3 receptor (H3R), a protein highly expressed in various neurological and psychiatric conditions. These cutting-edge tracers possess extended half-lives, overcoming the limitations of current PET agents primarily labeled with carbon-11, which has a rapid decay. This advancement promises to improve the scope and accuracy of brain imaging.
The research, presented at the 2025 Society of Nuclear Medicine and Molecular Imaging Annual Meeting and published in the Journal of Nuclear Medicine, highlights two promising compounds—H3-2401 and H3-2406—radiolabeled with fluorine-18. These compounds demonstrated high affinity for H3R, significant stability in vivo, and favorable pharmacokinetic profiles, making them suitable for broader clinical application.
H3R plays a crucial role in regulating histamine synthesis and release in the central nervous system, impacting vital functions like learning, memory, and sleep. Its inhibition has therapeutic potential for various brain disorders, making accurate detection of H3R distribution essential for drug development. Currently, only three H3R PET tracers are in clinical evaluation, all labeled with carbon-11, which limits their widespread use due to the short half-life.
The team from Emory University designed and synthesized a series of antagonists for H3R, selecting the best candidates—H3-2401 and H3-2406—for radiolabeling with fluorine-18. Evaluations across multiple species showed these tracers had excellent brain uptake, targeted binding, and improved stability compared to existing options. Their longer half-life of approximately 108 minutes further enhances their potential for clinical neuroimaging.
Dr. Zhendong Song from Emory emphasizes that these developments could pave the way for more effective brain imaging agents, especially for underexplored targets like H3R. Future research will focus on structural optimization and testing in models of neurodegenerative diseases such as Alzheimer's and Huntington’s disease.
This breakthrough in PET tracer technology could significantly improve the diagnosis and understanding of neurological and psychiatric conditions by enabling clearer, more reliable imaging of brain receptors involved in critical neural processes.
source: https://medicalxpress.com/news/2025-06-pet-tracers-advance-central-nervous.html
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