The goal of this observational study is to characterise the relationships between inflammation, microcalcification and thrombus activity in atherosclerotic plaques in peripheral and systemic vascular territories in patients with symptomatic peripheral arterial disease.
In peripheral arterial disease (PAD), arteries in the lower body can become narrowed and develop blockages due to a process called atherosclerosis, leading to reduced blood flow to the lower limbs. Symptoms can range from mild cramping pain in legs on walking, to loss of parts of the leg. Patients with PAD are also at a high risk of blockages in other arteries in the body that can lead to problems such as heart attacks and strokes. Despite improvements in medical treatments and surgery, the outlook for patients with PAD has not improved. Further information is required to understand the relationships between the processes that lead to narrowing and blockages (atherosclerosis) of the arteries and if they behave the same in different parts of the body. This can help to identify targeted treatments to reduce the risk of the disease getting worse and avoid heart attacks and strokes. In this study investigators plan to recruit 100 people with symptomatic PAD to undergo a series of whole body PET-CT and CT angiogram scans using different tracers targeting the processes involved in atherosclerosis. Investigators will aim to co-enrol patients taking part in the LEADER-PAD study (NCT04774159).
Study Type
OBSERVATIONAL
Enrollment
100
Targeting vascular inflammation
Targeting thrombus activity
Targeting vascular microcalcification
Royal Infirmary of Edinburgh
Edinburgh, Midlothian, United Kingdom
RECRUITINGQuantification of PET tracer uptake of [68Ga]DOTATATE, [18F]GP1 and [18F]NaF in the symptomatic lower limb(s)
The 3 primary endpoints will be the location and degree of: 1. inflammation: uptake of \[68Ga\]DOTATATE 2. calcification: uptake of \[18F\]NaF 3. thrombus activity: uptake of \[18F\]GP1 in peripheral arterial disease affecting the lower limbs. This will be determined by the degree of tracer standardised uptake values (SUVs) at the site of the symptomatic atherosclerotic plaque.
Time frame: From baseline imaging until completion imaging at 1 year
Quantification of PET tracer uptake of [68Ga]DOTATATE, [18F]GP1 and [18F]NaF in remote arterial territories
The secondary outcome measures will be the location and degree of inflammation, calcification and thrombus activity in remote arterial territories, including the coronary arteries, cerebral arteries, aorta and mesenteric vessels, as determined by SUVs of \[68Ga\]DOTATATE, \[18F\]NaF and \[18F\]GP1, respectively.
Time frame: From baseline imaging until completion imaging at 1 year
CT plaque morphology
Investigators will characterise CT plaque morphology (total, calcified, non-calcified and low-attenuation plaque) in peripheral and systemic arterial beds and compare this to areas of \[68Ga\]DOTATATE, \[18F\]GP1 and \[18F\]NaF uptake.
Time frame: From baseline imaging to completion imaging at 1 year
The association between patient risk factors for cardiovascular disease and PET tracer uptake
Investigators will explore the association between patient risk factors for cardiovascular disease (hypertension, diabetes, smoking) and the degree of \[68Ga\]DOTATATE, \[18F\]GP1 and \[18F\]NaF uptake as quantified by standard uptake values (SUVs). This will be measured by odds ratio (OR) with 95% confidence interval (CI) for each risk factor-tracer combination.
Time frame: Frome baseline imaging to completion imaging at 1 year
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To determine anatomical and morphological atherosclerotic plaque characteristics
The progression of microcalcification, as defined by [18F]NaF uptake, to macrocalcification.
Investigators will also aim to characterise the relationship between microcalcification progressing to calcification and the uptake of \[18F\]NaF. This will be assessed using baseline and follow-up \[18F\]NaF PET-CT SUVs and their correlation with calcified regions on CT angiography.
Time frame: From baseline imaging to completion imaging at 1 year