Abstract

Background/Objective: Angiogenesis is a complex process. Studies in aneurysmal aortic wall in human tissue and animal models have demonstrated an increased mural neovascularization, and Integrin αVβ3 is a molecular indicator of angiogenesis. We aim to study and characterize Integrin αVβ3 expression with Gallium-68(68Ga)-labeled Arg-Gly-Asp (RGD) as a potential radiotracer using micro Positron Emission Tomography (PET) in a Murine model of Thoracic Aortic Aneurysms (TAA). Methods: Eight specimens of Wistar rat with Calcium Chloride (CaCl) TAA-induced were evaluated. The equipment utilized was an Albira microPET/CT unit (Bruker, Spain), access was obtained in one of the caudal veins for the radiolabeled 68Ga-RGD infusion. The PET uptake and activity were expressed as median value with interquartile range and the Mann-Whitney U test was employed to analyze and compare the chemically induced-site (Aneurysm) and intact aortic tissue (Control) in the same specimens. Statistical analysis was performed with GraphPad Prism 8.0 software. Results: All specimens tolerated well the procedures through a left thoracotomy (Upper panel figure A, B), and underwent imaging studies. A focal increased uptake was observed in the thoracic aortic lesions compared to control regions. The median standard uptake value (SUV) of 68Ga-RGD in the chemically induced-injury site (aneurysm) was 0.0125, while the uptake in the intact site (control) was 0.0003 (P value=0.0117) during a mean follow up period of 32 days (Lower panel figure A-C). Conclusion: We found significant differences of Integrin αVβ3 expression uptake with microPET imaging in chemically induced aneurysms and the intact aortic tissue within 5 weeks of vessel injury. Longitudinal studies with this imaging modality may assist in the molecular characterization of angiogenesis and aneurysmal progression in animal models, and its potential translation in clinical research studies in human patients with aortic aneurysm.

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