Chantal Kopecky1, Elvis Pandzic2, Arvind Parmar3, Jeremy Szajer4, Victoria Lee1, Alexander Dupuy1, Andrew Arthur3, Sandra Fok2, Renee Whan2, William J Ryder4, Kerry-Anne Rye1, Blake J Cochran5. 1. School of Medical Sciences, Faculty of Medicine, UNSW Sydney, Sydney, Australia. 2. Biomedical Imaging Facility, Mark Wainwright Analytical Centre, UNSW Sydney, Sydney, Australia. 3. Australian Nuclear Science and Technology Organisation, Sydney, Australia. 4. Department of Nuclear Medicine, Concord Repatriation General Hospital, Sydney, Australia. 5. School of Medical Sciences, Faculty of Medicine, UNSW Sydney, Sydney, Australia. Electronic address: b.cochran@unsw.edu.au.
Abstract
BACKGROUND AND AIMS: Atherosclerosis is characterized by lipid deposition, monocyte infiltration and foam cell formation in the artery wall. Translocator protein (TSPO) is abundantly expressed in lipid rich tissues. Recently, TSPO has been identified as a potential diagnostic tool in cardiovascular disease. The purpose of this study was to determine if the TSPO ligand, 18F-PBR111, can identify early atherosclerotic lesions and if TSPO expression can be used to identify distinct macrophage populations during lesion progression. METHODS: ApoE-/- mice were maintained on a high-fat diet for 3 or 12 weeks. C57BL/6J mice maintained on chow diet served as controls. Mice were administered 18F-PBR111 intravenously and PET/CT imaged. After euthanasia, aortas were isolated, fixed and optically cleared. Cleared aortas were immunostained with DAPI, and fluorescently labelled with antibodies to TSPO, the tissue resident macrophage marker F4/80 and the monocyte-derived macrophage marker CD11b. TSPO expression and the macrophage markers were visualised in fatty streaks and established plaques by light sheet microscopy. RESULTS: While tissue resident F4/80 + macrophages were evident in the arteries of animals without atherosclerosis, no CD11b + macrophages were observed in these animals. In contrast, established plaques had high CD11b and low F4/80 expression. A ∼3-fold increase in the uptake of 18F-PBR111 was observed in the aortas of atherosclerotic mice relative to controls. CONCLUSIONS: Imaging of TSPO expression is a new approach for studying atherosclerotic lesion progression and inflammatory cell infiltration. The TSPO ligand, 18F-PBR111, is a potential clinical diagnostic tool for the detection and quantification of atherosclerotic lesion progression in humans.
BACKGROUND AND AIMS: Atherosclerosis is characterized by lipid deposition, monocyte infiltration and foam cell formation in the artery wall. Translocator protein (TSPO) is abundantly expressed in lipid rich tissues. Recently, TSPO has been identified as a potential diagnostic tool in cardiovascular disease. The purpose of this study was to determine if the TSPO ligand, 18F-PBR111, can identify early atherosclerotic lesions and if TSPO expression can be used to identify distinct macrophage populations during lesion progression. METHODS:ApoE-/- mice were maintained on a high-fat diet for 3 or 12 weeks. C57BL/6J mice maintained on chow diet served as controls. Mice were administered 18F-PBR111 intravenously and PET/CT imaged. After euthanasia, aortas were isolated, fixed and optically cleared. Cleared aortas were immunostained with DAPI, and fluorescently labelled with antibodies to TSPO, the tissue resident macrophage marker F4/80 and the monocyte-derived macrophage marker CD11b. TSPO expression and the macrophage markers were visualised in fatty streaks and established plaques by light sheet microscopy. RESULTS: While tissue resident F4/80 + macrophages were evident in the arteries of animals without atherosclerosis, no CD11b + macrophages were observed in these animals. In contrast, established plaques had high CD11b and low F4/80 expression. A ∼3-fold increase in the uptake of 18F-PBR111 was observed in the aortas of atheroscleroticmice relative to controls. CONCLUSIONS: Imaging of TSPO expression is a new approach for studying atherosclerotic lesion progression and inflammatory cell infiltration. The TSPO ligand, 18F-PBR111, is a potential clinical diagnostic tool for the detection and quantification of atherosclerotic lesion progression in humans.
Authors: Omkar L Patkar; Abdalla Z Mohamed; Ashwin Narayanan; Karine Mardon; Gary Cowin; Rajiv Bhalla; Damion H R Stimson; Michael Kassiou; Kate Beecher; Arnauld Belmer; Ignatius Alvarez Cooper; Michael Morgan; David A Hume; Katharine M Irvine; Selena E Bartlett; Fatima Nasrallah; Paul Cumming Journal: Sci Rep Date: 2021-05-27 Impact factor: 4.379
Authors: Zarni Win; January Weiner Rd; Allan Listanco; Neva Patel; Rohini Sharma; Aldona Greenwood; Jeroen Maertzdorf; Hans-Joachim Mollenkopf; Kat Pizzoferro; Thomas Cole; Caroline L Bodinham; Stefan H E Kaufmann; Philippe Denoel; Giuseppe Del Giudice; David J M Lewis Journal: Front Immunol Date: 2021-02-05 Impact factor: 7.561