Media Contact:
Rebecca Maxey
(703) 652-6772
[email protected]

 

New PET Radiotracer Provides First Look at Inflammation Biomarker in the Human Brain


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.

Figure 7. PET protein atlases for various [11C]MC1 positron PET imaging metrics targeting COX-2. (A and B) Distribution volume (VT) (A) and binding potential (BPND) (B) through volume-based analysis (left) and surface-based analysis (right) tailored to respect cortical geometry of the brain to enhance precision. (C) Between-subject variability for total COX-2 uptake, quantified as coefficient of variation, contrasting volumetric analysis (left) and surface-based analysis (right). Surface-based analysis respects the unique cortical geometry of individual participants (left), thereby reducing partial-volume effects. Moreover, a surface-based approach mitigates increased between-subject variability observed using volumetric analysis, which is exacerbated by differences in anatomy that lead to edge or boundary effects. By respecting cortical geometry, surface-based analysis reduces between-subject variability in the cortex, consequently lowering the number of participants needed in group analyses to detect similar statistical significance.

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.

 Visit the JNM website for the latest research, and follow our new Twitter and Facebook pages @JournalofNucMed or follow us on LinkedIn.

###

Please visit the SNMMI Media Centerfor more information about molecular imaging and precision imaging. To schedule an interview with the researchers, please contact Rebecca Maxey at (703) 652-6772 or [email protected].

 

 About JNM and the Society of Nuclear Medicine and Molecular Imaging

 The Journal of Nuclear Medicine (JNM) is the world’s leading nuclear medicine, molecular imaging and theranostics journal, accessed 15 million times each year by practitioners around the globe, providing them with the information they need to advance this rapidly expanding field. Current and past issues of The Journal of Nuclear Medicine can be found online at http://jnm.snmjournals.org.

JNM is published by the Society of Nuclear Medicine and Molecular Imaging (SNMMI), 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. For more information, visit www.snmmi.org.