Molecular imaging of abdominal aortic aneurysms

Abdominal aortic aneurysm (AAA) disease is characterised by an asymptomatic, permanent, focal dilatation of the abdominal aorta progressing towards rupture, which confers significant mortality. Patient management and surgical decisions currently rely on aortic diameter measurements via abdominal ultrasound screening. However, AAA rupture can occur at small diameters or may never occur at large diameters. Therefore, there is a need to develop molecular imaging-based biomarkers independent of aneurysm diameter that may help stratify patients with early-stage AAA to reduced surveillance. AAA uptake of [18F]fluorodeoxyglucose on positron emission tomography (PET) has been demonstrated previously; however, its glucose-dependent uptake may overlook other key mechanisms. The cell proliferation marker [18F]fluorothymidine ([18F]FLT) is primarily used in tumour imaging. The aim of the overall study for this thesis was to explore the feasibility of [18F]FLT PET / computed tomography (CT) to visualise and quantify AAA in the angiotensin II (AngII)-infused mouse model. The experiments presented in this thesis revealed increased uptake of [18F]FLT in the 14-day AngII AAA model than in saline controls, followed by a decrease in this uptake at 28 days. Moreover, in line with the in vivo PET/CT findings, Western blotting of aortic tissue revealed increased levels of thymidine kinase-1 (the substrate of [18F]FLT) and nucleoside transporters in the 14-day AngII AAA model than in saline controls, followed by decreased expression levels at 28 days. A pilot experiment further demonstrated that [18F]FLT PET/CT could be used to detect an early therapeutic response to oral imatinib treatment in the AngII AAA model. Therefore, [18F]FLT PET/CT may be a feasible modality to detect and quantify cell proliferation in the AngII AAA murine model. The findings of this thesis are encouraging for the application of [18F]FLT PET/CT in patients with small AAA.