Novel PET Imaging Approach Offers Never-Before-Seen View of Neuroinflammation

COX-2, an enzyme that plays a key role in brain inflammation, can be significantly upregulated by inflammatory stimuli and neuroexcitation. Researchers suggest that COX-2 density in the brain could serve as both a biomarker and an effect of inflammation, even if it is not directly responsible for the inflammatory process itself. Although COX-2 has been extensively studied in peripheral inflammation, quantifying its role in neuroinflammation in vivo has proven challenging. Now, a new PET imaging technique enables effective quantification of COX-2, according to research published in The Journal of Nuclear Medicine.

The first-in-human study conducted by researchers at the National Institutes of Health (NIH, Bethesda, MD, USA) has provided an unprecedented view of brain inflammation by imaging the COX-2 enzyme, paving the way for COX-2 PET imaging to be used in both clinical and research settings for various brain disorders. This research aimed to establish a non-invasive imaging technique to measure COX-2 in the living brain, facilitating earlier disease detection, monitoring disease progression, and evaluating anti-inflammatory treatments. The study specifically tested the ability of 11C-MC1 to quantify COX-2 levels in the healthy human brain.

The researchers first assessed 11C-MC1’s affinity for human COX-2 by conducting PET imaging in rats injected with lipopolysaccharide and in humanized transgenic COX-2 mice, confirming its specific binding to human COX-2. Following this, 27 healthy human volunteers were imaged using 11C-MC1 PET to measure COX-2 density in the human brain. The results showed that 11C-MC1 successfully crossed the blood-brain barrier, bound to its target, and demonstrated high specificity for human COX-2. The radiotracer also exhibited 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,” said Robert B. Innis, MD, PhD, senior investigator in the Molecular Imaging Branch of the National Institute of Mental Health at NIH. “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.”

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