Large Vessel Vasculitis: An Upcoming Target of PET Imaging

Introduction: Large vessel vasculitis is an inflammatory disease mainly affecting the large arteries, including Takayasu arteritis, giant cell arteritis (GCA), and polymyalgia rheumatica (PMR). Undiagnosed large vessel vasculitis could lead to devastating outcomes such as irreversible vision loss, aortic dissection, or cerebrovascular events. Although biopsy remains the gold standard for diagnosis, it is invasive and not always feasible. More recently, growing evidence has shown the ability of PET imaging in its diagnosis and treatment monitoring.

Methods: We reviewed multiple databases, including PubMed, Google Scholar, and compiled a comprehensive body of literatures related to the PET imaging used in large vessel vasculitis. Findings from multiple research papers were then analyzed and synthesized. We will discuss the evolving role of PET imaging in the diagnosis of large vessel vasculitis and monitor its treatment response.

Results: ¹⁸F-FDG is a well-studied radiotracer used in inflammatory disease and atherosclerosis. The advantages of ¹⁸F-FDG PET in large vessel vasculitis including correlation with disease activity and possible prediction of relapse after cessation of treatment. However, optimal preparation is necessary and its sensitivity is reduced in patients with glucocorticoid use, which is the mainstay medication in large vessel vasculitis. Therefore, with the improvement in the understanding of the immunopathogenesis of large vessel vasculitis, recent trend has shifted toward the radiotracers that targeting specific cellular populations. T cells are the major cells types in vasculitis. The first-generation IL-2 tracer, [¹⁸F] FB-IL-2, has demonstrated high binding affinity to activated human peripheral blood mononuclear cells; however, it may mask the detection of arterial inflammation in vasculitis. In contrast, second-generation IL-2 based tracers, [¹⁸F]AIF-RESCA-IL2 and [⁶⁸Ga] Ga-NODAGA-IL2 have showed no brain uptake and lower blood pool radioactivity compared to first generation. Nevertheless, human studies are needed to further evaluate its clinical utility. B-cell targeted imaging has been studied with proposed use in assessing GCA. Successful visualization of aortic and arterial inflammation has been demonstrated in the context of GCA using [⁶⁸Ga] FAPI-04 with negligible radioactivity in non-target organs, including the brain, background tissue, and in the blood pool, which may allow accurate detection of GCA. When it comes to monitoring the treatment efficacy, reduced numbers of T cells and macrophages at the site of inflammation have been reported. Hence, tracking the dynamics of these cellular markers by imaging may be useful for treatment effect determination.

Conclusions: While ¹⁸F-FDG is able to identify changes associated with large vessel vasculitis, emerging PET radiotracers could potentially be more accurate than ¹⁸F-FDG for the treatment monitoring as they may provide lower background radioactivity and higher diagnostic accuracy, improving the ability to assess treatment effectiveness. However, further clinical trials are needed to evaluate and confirm their utility in the diagnosis and monitoring of large vessel vasculitis.