image: Figure 1. Representative summed PET images of brain uptake under baseline and GSK189254-blocking (3 mg/kg prior to tracer injection) conditions.
Credit: Images created by Song Z, Liang S et al., Emory University, Atlanta, GA.
NEW ORLEANS (June 21, 2025)—Two newly developed PET imaging agents have been proven effective in identifying the histamine H3 receptor (H3R) that is highly expressed in neurological and psychiatric conditions. The novel agents have a long half-life, addressing key limitations of existing tracers and offering the potential to enable broader clinical imaging of H3R. This research was presented at the 2025 Society of Nuclear Medicine and Molecular Imaging Annual Meeting.
H3R regulates histamine synthesis and release in the central nervous system, which influences learning, memory, and sleep. H3R inhibition has shown therapeutic potential for treating a variety of brain disorders, and accurate detection of H3R expression and distribution is crucial for drug development.
“Currently, there are only three H3R PET tracers that have reached clinical evaluation—all of which are labeled with 11C. Since 11C has a very short half-life (approximately 20 minutes), the clinical utility of these tracers is greatly limited,” said Zhendong Song, PhD, postdoctoral fellow at Emory University in Atlanta, Georgia. “Our study sought to address these challenges by developing novel H3R PET tracers with enhanced target specificity and optimal tracer performance.”
A series of H3R antagonists were designed and synthesized, and binding affinity assays were conducted to identify the most promising candidates. The antagonists with the highest binding affinities—H3-2401 and H3-2406—were then radiolabeled with 18F for further evaluation.
The metabolic stability of 18F- H3-2401 and 18F- H3-2406 was assessed across multiple species (mice, non-human primates, and humans). Autoradiography, dynamic PET imaging, blocking studies, and ex vivo biodistribution studies were conducted in rodents to further evaluate their properties and potential for neuroimaging.
PET imaging with 18F- H3-2401 and 18F- H3-2406 revealed high brain uptake and excellent specificity. The probes also showed improved in vivo stability and favorable pharmokinetics. Furthermore, the 108 minutes half-life of these tracers was significantly higher than 11C tracers.
“This research offers a valuable reference for the rational design of future brain imaging agents, particularly for underexplored targets like H3R,” noted Steven Liang, PhD, director of PET Imaging at Emory University. “Future efforts will focus on structural optimization, followed by preclinical testing in Alzheimer’s and Huntington disease models.”
Abstract 251600. “Novel Histamine Subtype 3 Receptor (H3R) PET Ligands for Brain Imaging,” Zhendong Song, Li Yinlong, Ahmad, Chaudhary, and Steven Laing, Emory University, Atlanta, Georgia, and Kenneth Dahl, Chad Elmore, and Magnus Schou AstraZeneca.
Link to Abstract
###
All 2025 SNMMI Annual Meeting abstracts can be found online.
About the Society of Nuclear Medicine and Molecular Imaging
The Society of Nuclear Medicine and Molecular Imaging (SNMMI) is an international scientific and medical organization dedicated to advancing nuclear medicine, molecular imaging, and theranostics—precision medicine that allows diagnosis and treatment to be tailored to individual patients in order to achieve the best possible outcomes.
SNMMI’s members set the standard for molecular imaging and nuclear medicine practice by creating guidelines, sharing information through journals and meetings and leading advocacy on key issues that affect molecular imaging and therapy research and practice. For more information, visit www.snmmi.org.
Journal
Journal of Nuclear Medicine
Article Title
Novel Histamine Subtype 3 Receptor (H3R) PET Ligands for Brain Imaging