(Press-News.org) Reston, VA (March 28, 2025)—A novel PET imaging approach can effectively quantify a key enzyme associated with brain inflammation, according to research published in the March issue of The Journal of Nuclear Medicine. The first-in-human study, which imaged the COX-2 enzyme, offers a never-before-seen view of inflammation in the brain, opening the door for COX-2 PET imaging to be used in clinical and research settings for various brain disorders.
COX-2 is an enzyme in the brain that can be markedly upregulated by inflammatory stimuli and neuroexcitation. Researchers say that the density of COX-2 in the brain may be a biomarker and effect of inflammation, even if it is not a mediator of the inflammatory process.
“While COX-2 has been widely studied in peripheral inflammation, its role in neuroinflammation has been difficult to quantify in vivo,” stated Robert B. Innis, MD, PhD, senior investigator in the Molecular Imaging Branch of the National Institute of Mental Health at the National Institutes of Health in Bethesda, Maryland. “We sought to establish a non-invasive imaging method to measure COX-2 in the living brain to enable earlier disease detection, monitor disease progression, and assess anti-inflammatory treatments.”
This study evaluated the ability of 11C-MC1 to measure COX-2 levels in the healthy human brain. First, 11C-MC1’s affinity for human COX-2 was assessed by conducting PET imaging in rats injected with lipopolysaccharide and in humanized transgenic COX-2 mice. Specific binding to human COX-2 was confirmed. Subsequently, 27 healthy human volunteers were imaged with 11C-MC1 PET to quantify the density of COX-2 in the human brain.
Among study participants, 11C-MC1 efficiently crossed the blood–brain barrier, bound to its designated target, and demonstrated high specificity for human COX-2. The radiotracer also had a moderate ratio of specific to background uptake binding potential in cortical regions.
“Neuroinflammation plays a critical role in many neurological and psychiatric diseases, including Alzheimer’s disease, Parkinson’s disease, and major depressive disorder,” noted Innis. “This could be a game-changer for personalized medicine and therapeutic development. It also demonstrates the potential for developing other PET tracers to investigate neuroinflammation, broadening the applications of nuclear medicine in neurology and psychiatry.”
Research reported in this press release was supported by the National Institute of Mental Health of the National Institutes of Health under award 1ZIAMH002852-20.
The authors of “PET Quantification in Healthy Humans of Cyclooxygenase-2, a Potential Biomarker of Neuroinflammation” include Xuefeng Yan, Cheryl L. Morse, Jeih-San Liow, Jinsoo Hong, Sanjay Telu, Min-Jeong Kim, Jose A. Montero Santamaria, Anthony Galassi, Ningping Feng, Sarah K. Williams Avram, Ted B. Usdin, Shawn Wu, Andrea Zhang, Lester S. Manly, Madeline Jenkins, Maia Van Buskirk, Adrian Lee, Sami S. Zoghbi, Victor W. Pike, Paolo Zanotti-Fregonara, and Robert B. Innis, Intramural Research Program, National Institute of Mental Health, Bethesda, Maryland; Martin Noergaard, Intramural Research Program, National Institute of Mental Health, Bethesda, Maryland, and Department of Computer Science, University of Copenhagen, Copenhagen, Denmark; and Douglas Greve, Laboratory for Computational Neuroimaging, Athinoula A. Martinos Center for Biomedical Imaging, Charlestown, Massachusetts.
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New PET radiotracer provides first look at inflammation biomarker in the human brain
2025-03-28
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