Antineutrophil cytoplasm antibody (ANCA)-associated vasculitis (AAV) is a severe autoimmune condition characterised by inflammation of small blood vessels. The condition causes multi-organ dysfunction and, if left untreated, is usually fatal. AAV is difficult to diagnose and the degree of disease activity is challenging to monitor. Current methods of disease activity assessment are either inaccurate (blood tests), invasive (biopsy), or non-specific (imaging). Additionally, though modern treatments are effective, patients with AAV remain at a substantially increased risk of cardiovascular disease (CVD) in the long-term. There is therefore an urgent need for a tool which is able to reliably identify disease, and assess long-term CVD risk.
Total-Body PET imaging with FDG, DOTATATE, and FAPI radiotracers may provide the answer. This study will recruit patients with active AAV, together with a control group of individuals without the disease, to undergo Total-Body FDG, DOTATATE, and FAPI PET scanning and compare the results with established measures of disease activity and CVD risk assessment.
The investigators believe that Total-Body PET scanning will be capable of accurately identifying AAV disease and those at increased CVD risk. This could enhance understanding and improve the management of those with the condition.
This study will recruit a group of patients with AAV and a comparator groups of 'matched' individuals without AAV. Comparisons between groups will allow the investigators to ensure that the changes seen are due to AAV disease. The study will recruit a minimum of 30 and a maximum of 90 participants in the AAV group, and a minimum of 10 and maximum of 30 participants in the matched control group.
AAV subjects and matched control subjects will undergo baseline total-body PET scanning with either one, two or three radiotracers (\[18F\]-FDG, \[68Ga\]-DOTATATE, and \[68Ga\]-FAPI). Alongside this they will receive assessment of cardiovascular disease risk including 24-hour blood pressure measurement, arterial stiffness measurement, and retinal scanning. Participants will also supply a blood and urine sample.
For matched control subjects, their participation will end at this point. Subjects in the AAV group will undergo repeat assessment with total-body PET imaging and cardiovascular disease risk measurement once their condition is in remission (usually after around 3-6 months).
The investigators will compare PET scan results between groups, and with cardiovascular assessments. This will allow determination of whether total-body PET scanning can identify AAV disease activity, and whether it can inform CVD risk.
All research activity will be carried out within the University of Edinburgh BioQuarter, including the Royal infirmary of Edinburgh, the Edinburgh Imaging Facility, and Queen's Medical Research Institute.
18+ years of age
Diagnosis of active AAV (AAV group)
Outwith early treatment window (must receive baseline scan <3 weeks from starting treatment)
Pregnancy or breastfeeding
Advanced renal dysfunction (eGFR <15ml/min/1.73m2)
Adverse reaction or hypersensitivity to proposed radiotracers
AAV group: all participants will have a diagnosis of ANCA-associated vasculitis (AAV) in accordance with the 2012 Revised International Chapel Hill Consensus Conference Nomenclature of Vasculitides criteria and clinician's assessment. At enrolment, participants in the AAV group will have active disease, as defined by the presence of symptoms and signs attributable to active vasculitis necessitating the commencement or increase in immunosuppressive treatment other than glucocorticoids. Matched control group: all participants will be matched with the AAV group based on age, gender, ethnicity, and cardiovascular disease risk factors including impaired kidney function. They will have no additional health problems and be taking no additional medications (other than those relevant to cardiovascular disease risk) that may interfere with PET imaging.
Case-control
Prospective
Not listed
Change in tracer ([18F]-FDG, [68Ga]-DOTATATE, and [68Ga]-FAPI) uptake (calculated using maximum standardised uptake values (SUVmax)) within regions of interest between baseline and remission)
The change in PET radiotracer uptake within regions of interest between patients with active AAV (e.g. at baseline) and patients in remission (e.g. at follow-up)
Correlation between tracer uptake (SUVmax and SUVmean) and established measures of disease activity including: o CRP o ANCA titre o Patient reported disease activity o Physician estimated disease activity
As above
Correlation between tracer uptake (SUVmax and SUVmean) and established surrogate measures of CVD risk including: o Arterial stiffness o 24-hour ambulatory blood pressure o Retinal OCT imaging metrics
As above
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