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Background <p>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.</p> Objective <p>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.</p> Methods <p>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 (<a href="https://doi.org/10.17605/OSF.IO/RGM6B">https://doi.org/10.17605/OSF.IO/RGM6B</a>).</p> Results <p>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.</p> Conclusion <p>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.</p>

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Imaging the neuroinflammatory landscape: COX enzyme mapping with PET

  • 期刊论文

  • 发表日期：

    2025年6月12日

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  • Atena Asghari,
  • Dina Seyedi,
  • Helia Sadat Kazemi,
  • Vesal Abbasian,
  • Sayedeh-Fatemeh Sadat-Madani,
  • Mostafa Bahmanziari,
  • Zahra Asadian,
  • Shirin Salehkheil,
  • Anis Mahdavipour,
  • Elham Habibzadeh,
  • Pouya Asgari,
  • Mahsa Asadi Anar,
  • Reza Daghayeghi,
  • Ghazaleh Elahabadi

摘要

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.