Imaging the neuroinflammatory landscape: COX enzyme mapping with PET

Abstract

BackgroundCyclooxygenase-1 (COX-1) and Cyclooxygenase-2 (COX-2) are key enzymes in the neuroinflammatory cascade, representing promising targets for in vivo brain imaging using positron emission tomography (PET). However, the translational utility of COX-specific PET radiotracers remains incompletely understood, and a cohesive brain imaging atlas of COX expression is lacking.ObjectiveThis review aimed to synthesize current evidence on PET imaging of COX-1 and COX-2 in the brain and evaluate the characteristics, performance, and clinical applicability of available radiotracers to support the development of a Molecular Imaging Brain Atlas (MIBA) for COX enzymes.MethodsA comprehensive literature search was performed through PubMed, Scopus, and Web of Science up to March 2025. Studies were included if they reported in vivo PET imaging of COX-1 or COX-2 in animal or human brains using selective radiotracers. Data extraction focused on tracer selectivity, binding kinetics, brain uptake, and inflammation-specific imaging outcomes. The protocol was registered in OSF (https://doi.org/10.17605/OSF.IO/RGM6B).ResultsTwenty studies met the inclusion criteria. C-1(1)PS13 emerged as the most validated COX-1 tracer in both preclinical and human studies, while C-1(1)MC1 demonstrated inducible binding to COX-2 under inflammatory conditions. Fluorine-18-labeled tracers such as F-1(8)FKTP-Me and F-1(8)PS13 showed promise for clinical scalability.ConclusionSubstantial progress has been made in COX-targeted PET imaging, particularly for COX-1. Continued tracer optimization, quantitative standardization, and disease-specific validation are essential to developing a robust atlas of COX distribution in the brain and advancing neuroinflammation research.