PET Assessment of Disease Activity and Cardiovascular Disease Risk in ANCA-associated Vasculitis

Antineutrophil cytoplasm antibody (ANCA)-associated vasculitis (AAV) is a rare condition which causes widespread blood vessel inflammation, leading to dysfunction in several organs. The condition is autoimmune, meaning that it is driven by an abnormal response from the body's own immune system, though the exact cause is unknown. Without treatment most patients with AAV will die. However current treatment is effective, with \~90% of patients alive at 1-year following diagnosis. Once the initial phase of the disease is controlled, patients remain at risk of relapse which can be difficult to detect. Additionally, in the long term, patients remain at an increased risk of death as a result of cardiovascular disease (CVD), including heart attacks and strokes.

The diagnosis of AAV is challenging and often delayed, meaning established organ damage is often present at diagnosis. Accurate assessment of disease activity is essential to guide best treatment in AAV. Smouldering, unchecked inflammation contributes to morbidity and to the development of CVD. Conversely, attributing symptoms to active disease when they are due to established injury risks overtreatment and associated side effects, which can be significant.

Current methods of disease activity assessment are limited. Biopsy is considered the gold standard, however, can only assess disease in one organ at a time, and is an invasive and unpleasant test. Several scans are currently available, though each is also limited in terms of coverage and accuracy. Accordingly, new methods of disease activity assessment are required which provide an accurate, non-invasive, and multi-system approach, both at presentation and throughout the disease course.

Additionally, even when disease control is optimum, patients with AAV remain at an increased risk of CVD. Methods to identify those at the highest risk of CVD events are lacking, thus personalising preventative therapies remains a challenge. Tools that can highlight those at an increased risk of CVD events are urgently needed.

Total-Body positron emission tomography (PET) scanning provides a potential solution to both of these problems.

PET scanning allows detection and quantification of disease within the body. With the advent of Total-Body PET facilities, scans now benefit from enhanced coverage, accuracy, and speed. Patients can now be reliably scanned from 'top to toe' relatively quickly, and with an acceptable degree of radiation exposure. Despite being used in several similar conditions, PET has never been adequately assessed in AAV.

PET scanning requires the injection of a 'radiotracer' which binds to areas of disease and can then be picked up by the scanner. Historically, we have used a radiotracer called FDG, however a number of newer radiotracers are now available which may be more accurate. The radiotracer DOTATATE may bind more specifically to the inflammation caused by AAV, allowing a more accurate picture of the disease to be painted. Additionally, the radiotracer FAPI finds to areas of fibrosis, or scarring. this radiotracer therefore has the potential to tell us about a different aspect of the disease, and help differentiate active inflammation from tissue damage and remodelling.

Finally, in addition to identifying active AAV disease, both FDG and DOTATATE may be able to inform which patients are more at risk of developing CVD in the future.

Accordingly, this study aims to assess the ability of Total-Body PET scanning, using three different radiotracers, to accurately assess disease activity in AAV, and identify those patients at an increased risk of CVD in the long term. This would improve outcomes for these patients, and increase understanding of the condition.