Macrophages are key players in the pathogenesis of large-vessel vasculitis (LVV) and may serve as a target for diagnostic imaging of LVV. The radiotracer, 18F-FDG has proven to be useful in the diagnosis of giant cell arteritis (GCA), a form of LVV

 

The human blood vessel system is one of the largest organ systems in the human body. As part of the cardiovascular system, the blood vessel system functions by distributing blood cells, oxygen and nutrients to, as well as expelling waste such as carbon dioxide from, all organs and tissues.

Separately, in the lymphoid system, blood vessels act as the transit site of lymphoid and myeloid cells of the immune system. Given the importance of blood vessels, inflammation of the vessels (vasculitis) can have major health consequences.

Nuclear imaging is currently gaining importance as a non-invasive tool for the diagnosis and monitoring of vascular inflammation. The application of nuclear imaging in the detection of LVV was initially a serendipitous discovery by Blockmans.

Macrophages have been recognized as key cellular players in the pathogenesis of LVV. Circulating monocytes are recruited to vasculitic lesions where they are activated and differentiate into macrophages.

Imaging inflammation

These activated macrophages produce pro-inflammatory cytokines and chemokines which amplify the inflammatory response and induce vascular remodeling. 18F-FDG PET as a tool for imaging inflammation has already proven to be useful for early diagnosis of LVV.

Although uptake of 18F-FDG is high in activated macrophages, it is not a specific radiotracer as its uptake is high in any proliferating cell and other activated immune cells resulting in high non-specific background radioactivity especially in aging and atherosclerotic vessels which dramatically lowers the diagnostic accuracy.

Evidence also exists that the sensitivity of 18F-FDG PET drops in patients upon glucocorticoid treatment. Therefore, there is a clinical need for more specific radiotracers in imaging GCA to improve diagnostic accuracy. Numerous clinically established and newly developed macrophage-targeted radiotracers for oncological and inflammatory diseases can potentially be utilized for LVV imaging.

These tracers are more target specific and therefore may provide lower background radioactivity, higher diagnostic accuracy and the ability to assess treatment effectiveness. However, current knowledge regarding macrophage subsets in LVV lesions is limited.

Further understanding regarding macrophage subsets in vasculitis lesion is needed for better selection of tracers and new targets for tracer development. This review summarizes the development of macrophage-targeted tracers in the last decade and the potential application of macrophage-targeted tracers currently used in other inflammatory diseases in imaging LVV.