Cyclooxygenases as Potential PET Imaging Biomarkers to Explore Neuroinflammation in Dementia

The most frequently studied target of neuroinflammation using PET is 18-kDa translocator protein, but its limitations have spurred the molecular imaging community to find more promising targets. This article reviews the development of PET radioligands for cyclooxygenase (COX) subtypes 1 and 2, enzymes that catalyze the production of inflammatory prostanoids in the periphery and brain. Although both isozymes produce the same precursor compound, prostaglandin H₂, they have distinct functions based on their differential cellular localization in the periphery and brain. For example, COX-1 is located primarily in microglia, a resident inflammatory cell in the brain whose role in producing inflammatory cytokines is well documented. In contrast, COX-2 is located primarily in neurons and can be markedly upregulated by inflammatory and excitatory stimuli, but its functions are poorly understood. This article reviews these 2 isozymes as biomarkers of neuroinflammation, as well as the radioligands that have recently been developed to image them in animals and humans. To place this work into context, the properties of COX-1 and COX-2 are compared with 18-kDa translocator protein, with special consideration of their application in Alzheimer disease as a representative neurodegenerative disorder.