Ambros J Beer1, Jaroslav Pelisek2, Peter Heider2, Antti Saraste3, Christian Reeps2, Stephan Metz4, Stefan Seidl5, Horst Kessler6, Hans-Jürgen Wester7, Hans Henning Eckstein2, Markus Schwaiger8. 1. Department of Nuclear Medicine, Technische Universität München, Munich, Germany. Electronic address: ambros.beer@tum.de. 2. Department of Vascular Surgery, Technische Universität München, Munich, Germany. 3. Turku PET Centre and Department of Cardiology, Turku, Finland. 4. Department of Radiology, Technische Universität München, Munich, Germany. 5. Department of Pathology, Helmholtz Zentrum München, Neuherberg, Germany. 6. Institute for Advanced Study and Center of Integrated Protein Science, Technische Universität München, Department Chemie, Garching, Germany; Chemistry Department, Faculty of Science, King Abdulaziz University, Jeddah, Saudi Arabia. 7. Chair of Pharmaceutical Radiochemistry, Technische Universität München, Garching, Germany. 8. Department of Nuclear Medicine, Technische Universität München, Munich, Germany.
Abstract
OBJECTIVES: The goal of this study was to evaluate the feasibility of [(18)F]Galacto-RGD positron emission tomography (PET)/computed tomography (CT) imaging of αvβ3 expression in human carotid plaques. BACKGROUND: The integrin αvβ3 is expressed by macrophages and angiogenic endothelial cells in atherosclerotic lesions and thus is a marker of plaque inflammation and, potentially, of plaque vulnerability. [(18)F]Galacto-RGD is a PET tracer binding specifically to αvβ3. Therefore, [(18)F]Galacto-RGD PET/CT imaging of αvβ3 expression in human carotid plaques might provide a novel noninvasive biomarker of plaque vulnerability. METHODS: [(18)F]Galacto-RGD PET/CT imaging was performed in 10 patients with high-grade carotid artery stenosis scheduled for carotid endarterectomy. Tracer uptake was measured in the stenotic areas of the carotid arteries, as well as on the contralateral side, and was corrected for blood pool activity, measured in the distal common carotid artery (target-to-background [TB] ratio). TB ratio was correlated with immunohistochemistry of αvβ3 expression (LM609), macrophage density (CD68), and microvessel density (CD31) of the surgical specimen. In addition, ex vivo autoradiography of the surgical specimen with [(18)F]Galacto-RGD and competition experiments with an unlabeled αvβ3-specific RGD peptide were performed. RESULTS: [(18)F]Galacto-RGD PET/CT showed significantly higher TB ratios in stenotic areas compared with nonstenotic areas (p = 0.01). TB ratios correlated significantly with αvβ3 expression (R = 0.787, p = 0.026) and intensity of ex vivo autoradiography (R = 0.733, p = 0.038). Binding to atherosclerotic plaques was efficiently blocked in ex vivo competition experiments. A weak-to-moderate correlation was found with macrophage density (R = 0.367, p = 0.299) and microvessel density (R = 0.479, p = 0.176), which did not reach statistical significance. CONCLUSIONS: [(18)F]Galacto-RGD PET/CT shows specific tracer accumulation in human atherosclerotic carotid plaques, which correlates with αvβ3 expression. Based on these initial data, larger prospective studies are now warranted to evaluate the potential of molecular imaging of αvβ3 expression for assessment of plaque inflammation in patients.
OBJECTIVES: The goal of this study was to evaluate the feasibility of [(18)F]Galacto-RGD positron emission tomography (PET)/computed tomography (CT) imaging of αvβ3 expression in human carotid plaques. BACKGROUND: The integrin αvβ3 is expressed by macrophages and angiogenic endothelial cells in atherosclerotic lesions and thus is a marker of plaque inflammation and, potentially, of plaque vulnerability. [(18)F]Galacto-RGD is a PET tracer binding specifically to αvβ3. Therefore, [(18)F]Galacto-RGD PET/CT imaging of αvβ3 expression in human carotid plaques might provide a novel noninvasive biomarker of plaque vulnerability. METHODS: [(18)F]Galacto-RGD PET/CT imaging was performed in 10 patients with high-grade carotid artery stenosis scheduled for carotid endarterectomy. Tracer uptake was measured in the stenotic areas of the carotid arteries, as well as on the contralateral side, and was corrected for blood pool activity, measured in the distal common carotid artery (target-to-background [TB] ratio). TB ratio was correlated with immunohistochemistry of αvβ3 expression (LM609), macrophage density (CD68), and microvessel density (CD31) of the surgical specimen. In addition, ex vivo autoradiography of the surgical specimen with [(18)F]Galacto-RGD and competition experiments with an unlabeled αvβ3-specific RGD peptide were performed. RESULTS: [(18)F]Galacto-RGD PET/CT showed significantly higher TB ratios in stenotic areas compared with nonstenotic areas (p = 0.01). TB ratios correlated significantly with αvβ3 expression (R = 0.787, p = 0.026) and intensity of ex vivo autoradiography (R = 0.733, p = 0.038). Binding to atherosclerotic plaques was efficiently blocked in ex vivo competition experiments. A weak-to-moderate correlation was found with macrophage density (R = 0.367, p = 0.299) and microvessel density (R = 0.479, p = 0.176), which did not reach statistical significance. CONCLUSIONS: [(18)F]Galacto-RGD PET/CT shows specific tracer accumulation in humanatherosclerotic carotid plaques, which correlates with αvβ3 expression. Based on these initial data, larger prospective studies are now warranted to evaluate the potential of molecular imaging of αvβ3 expression for assessment of plaque inflammation in patients.
Authors: Amr Alaarg; Carlos Pérez-Medina; Josbert M Metselaar; Matthias Nahrendorf; Zahi A Fayad; Gert Storm; Willem J M Mulder Journal: Adv Drug Deliv Rev Date: 2017-05-12 Impact factor: 15.470