Imaging the Neuroinflammatory Landscape: Cox Enzyme Mapping With Pet Publisher



A Asghari ATENA ; D Seyedi DINA ; Hs Kazemi Helia SADAT ; V Abbasian VESAL ; Sf Sadatmadani Sayedeh FATEMEH ; M Bahmanziari MOSTAFA ; Z Asadian ZAHRA ; S Salehkheil SHIRIN ; A Mahdavipour ANIS ; E Habibzadeh ELHAM
Source: Clinical and Translational Imaging Published:2025

Abstract

Background: Cyclooxygenase-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. Objective: This 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. Methods: A 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). Results: Twenty studies met the inclusion criteria. [¹¹C]PS13 emerged as the most validated COX-1 tracer in both preclinical and human studies, while [¹¹C]MC1 demonstrated inducible binding to COX-2 under inflammatory conditions. Fluorine-18-labeled tracers such as [¹⁸F]FKTP-Me and [¹⁸F]PS13 showed promise for clinical scalability. Conclusion: Substantial 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. © 2025 Elsevier B.V., All rights reserved.