Background. Abdominal aortic aneurysm (AAA) is a focal aortic dilatation progressing towards rupture. Non-invasive AAA-associated cell proliferation biomarkers are not yet established. We investigated the feasibility of the cell proliferation radiotracer, fluorine-18fluorothymidine ([ 18 F]FLT) with positron emission tomography/computed tomography (PET/ CT) in a progressive pre-clinical AAA model (angiotensin II, AngII infusion).

Abdominal aortic aneurysm (AAA) disease is characterized by an asymptomatic, permanent, focal dilatation of the abdominal aorta progressing towards rupture, which confers significant mortality. Patient management and surgical decisions rely on aortic diameter measurements via abdominal ultrasound surveillance. However, AAA rupture can occur at small diameters or may never occur at large diameters, implying that anatomical size is not necessarily a sufficient indicator. Molecular imaging may help identify high-risk patients through AAA evaluation independent of aneurysm size, and there is the question of the potential role of positron emission tomography (PET) and emerging role of novel radiotracers for AAA. Therefore, this review summarizes PET studies conducted in the last 10 years and discusses the usefulness of PET radiotracers for AAA risk stratification. The most frequently reported radiotracer was [18F]fluorodeoxyglucose, indicating inflammatory activity and reflecting the biomechanical properties of AAA. Emerging radiotracers include [18F]-labeled sodium fluoride, a calcification marker, [64Cu]DOTA-ECL1i, an indicator of chemokine receptor type 2 expression, and [18F]fluorothymidine, a marker of cell proliferation. For novel radiotracers, preliminary trials in patients are warranted before their widespread clinical implementation. AAA rupture risk is challenging to evaluate; therefore, clinicians may benefit from PET-based risk assessment to guide patient management and surgical decisions.

Abdominal aortic aneurysm (AAA) is a focal dilation of the aorta associated with high mortality through rupture. Most of our understanding of the biology that drives AAA progression originates from surgical samples acquired in cases of elective open repair. These markers, which include macrophage infiltration and angiogenesis, have led to the exploration of novel radiopharmaceuticals to study AAA in preclinical models and human patients. Current clinical practice to detect AAA involves ultrasound-based screening and surveillance. Although ultrasound is cheap and without radiation risk, aortic diameter does not predict the heterogenous growth of AAA between patients. Positron emission tomography takes advantage of novel radiolabeled markers of disease to track biological changes. In human trials, the role of 2-[ 18 F]-fluorodeoxyglucose in detecting aneurysm growth and outcome is still debated, whereas sodium [ 18 F]-fluoride (microcalcification) has been shown to predict AAA growth and clinical outcome. Murine studies have been used to assess the suitability of radiotracers detecting inflammation, angiogenesis, and proliferation. However, in the absence of human data, the clinical suitability and applicability of these tracers remain speculative. This review examines how markers of AAA change over time and the ability of positron emission tomography to track these changes and discusses the radiopharmaceuticals that could have an application in stratifying AAA subjects.

The porcine pancreatic elastase (PPE) model is a common preclinical model of abdominal aortic aneurysms (AAA). Some notable characteristics of this model include the low aortic rupture rate, non-progressive disease course, and infra-renal AAA formation. Enhanced [18F]fluorothymidine ([18F]FLT) uptake on positron emission tomography/computed tomography (PET/CT) has previously been reported in the angiotensin II-induced murine model of AAA. Here, we report our preliminary findings of investigating [18F]FLT uptake in the PPE murine model of AAA. [18F]FLT uptake was found to be substantially increased in the abdominal areas recovering from the surgery, whilst it was not found to be significantly increased within the PPE-induced AAA, as confirmed using in vivo PET/CT and ex vivo whole-organ gamma counting (PPE, n = 7; controls, n = 3). This finding suggests that the [18F]FLT may not be an appropriate radiotracer for this specific AAA model, and further studies with larger sample sizes are warranted to elucidate the pathobiology contributing to the reduced uptake of [18F]FLT in this model.