Preclinical and Clinical Molecular Imaging of Inflammation and Angiogenesis of the Vulnerable Atherosclerotic Plaque

Buissink, J.W. (Jouke Wisse) (2013) Preclinical and Clinical Molecular Imaging of Inflammation and Angiogenesis of the Vulnerable Atherosclerotic Plaque. thesis, Medicine.

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Abstract

Background: Cardiovascular disease (CVD) is the underlying cause of death in 50% of deaths in developed countries. This is mostly due to the increasing incidence of atherosclerosis. Atherosclerosis is a disease characterized by the thickening of the arterial wall due to cholesterol deposits. In this process inflammation, thrombosis and angiogenesis play a key role. Currently a patients CVD risk assement is based on the amount of vascular lumen stenosis, however most cardiovascular events occur as a consequence of a rupture in a non-stenotic atherosclerotic plaque. This calls for a new approach, aimed at visualizing the components that make a plaque vulnerable, e.g. inflammation and angiogenesis. The accurate detection and intervention of plaques that are prone to rupture might significantly decrease morbidity and mortality in patients. In this research we aim to investigate the feasibility of molecular imaging in detecting inflammation and angiogenesis in atherosclerotic plaques. Methods: ApoE mice were injected with 18FDG or 18F-RGD and scanned using a microPET scanner to determine the 18FDG or 18F-RGD uptake in their aorta. Fresh carotid endarterectomy (CEA) specimens were analyzed for angiogenesis using a microPET scanner. Twenty patient scans of patients who underwent an 18FDG PET/CT scan in the UMCG were analyzed for calcification and 18FDG uptake in the carotid artery. Results: 18FDG and 18F-RGD microPET scans were performed on athersclerotic apoE mice. We found heterogeneous uptake of 18FDG along their aorta, with a good target-to-background ratio in the thoracic area. 18F-RGD imaging of apoE mice did not depict atherosclerosis, and high bone uptake was observed. When scanning 18F-RGD incubated CEA specimens under the microPET scanner the results show good, heterogeneous uptake along the CEA specimen. In all specimens distinct hotspots were visible. Human 18FDG PET/CT scan analysis shows a high association between CVD and 18FDG uptake in the carotid region, however this was not significant. Conclusion: This study shows that 18FDG PET is feasible in demonstrating inflammation in vivo in both mouse and human atherosclerotic plaques. We also demonstrate that 18F-RGD PET depicts angiogenesis ex vivo in CEA specimens, but is not feasable in demonstrating angiogenesis in vivo in ApoE mice. Furthermore, we demonstrate that 18FDG uptake in the carotid region, measured by 18FDGPET/CT scan, is associated with CVD. Taken together, 18FDG PET/CT scan is a potential tool for clinically diagnosing atherosclerosis and stratifying patients’ risks for CVD.

Item Type:	Thesis (Thesis)
Supervisor name:	Supervised by: and Slart, Riemer MD PhD and Department of Nuclear Medicine and Molecular Imaging and University Medical Center Groningen
Faculty:	Medical Sciences
Date Deposited:	25 Jun 2020 10:54
Last Modified:	25 Jun 2020 10:54
URI:	https://umcg.studenttheses.ub.rug.nl/id/eprint/1456

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