title: Multi-radionuclide digital autoradiography of the intra-aortic atherosclerotic plaques using a monoclonal antibody targeting oxidized low-density lipoprotein.
abstract: The aim of this study was to use multi-radionuclide autoradiography to compare the different distributions of three radiolabelled tracers in an atherosclerotic mouse model. This method, along with immunohistochemistry, was applied to investigate the intra-aortic distribution of 2-deoxy-2-[(18)F]fluoro-D-glucose ((18)F-FDG), (131)I/(125)I labeled anti-oxidized Low Density Lipoprotein (oxLDL), and non-binding control antibodies. Aortas were isolated from a total of 12 apoB-100/LDL receptor deficient mice 73 h post injection of radioiodine-labeled anti-oxLDL and control antibody and 1 h post injection of (18)F-FDG. A solid-state real-time digital autoradiography system was used to image the slide mounted aortas. Contributions from each radionuclide were separated by half-life and emission energy and the aortas were subsequently stained with Oil Red O for plaque to aorta contrast ratios. Immunohistochemical staining was performed to detect anti-oxLDL and control antibody localization. Radiolabeled anti-oxLDL showed increased total activity uptake in the aorta over control antibody and immunohistochemical analysis of plaques indicated increased binding of the specific antibody compared to control. The intra-aortic activity distribution of the anti-oxLDL antibody was however very similar to that of the control antibody although both had higher atherosclerotic plaques to aorta wall ratios than (18)F-FDG. Given the right choice of radionuclides, multi-radionuclide digital autoradiography can be employed to compare several tracers ex vivo in the same animal. The distribution of anti-oxLDL antibodies did not significantly differ from the control antibody but it did appear to have a better plaque to aorta contrast at 73 h post injection than (18)F-FDG at 1 h post injection.
authors.affiliation: Department of Medical Radiation Physics, Lund University Lund, Sweden.
authors.forename: Anders
authors.initials: A
authors.lastname: Orbom
authors.affiliation: Bioinvent International AB Lund, Sweden.
authors.forename: Bo
authors.initials: B
authors.lastname: Jansson
authors.affiliation: Experimental Cardiovascular Research Unit, Department of Clinical Sciences, Skåne University Hospital Malmö, Lund University Sweden ; Cardiology Clinic, Skåne University Hospital Malmö Sweden.
authors.forename: Alexandru
authors.initials: A
authors.lastname: Schiopu
authors.affiliation: Division of Urological Cancers, Department of Clinical Sciences, Skåne University Hospital Malmö, Lund University Malmö, Sweden.
authors.forename: Susan
authors.initials: S
authors.lastname: Evans-Axelsson
authors.affiliation: Experimental Cardiovascular Research Unit, Department of Clinical Sciences, Skåne University Hospital Malmö, Lund University Sweden.
authors.forename: Jan
authors.initials: J
authors.lastname: Nilsson
authors.affiliation: Experimental Cardiovascular Research Unit, Department of Clinical Sciences, Skåne University Hospital Malmö, Lund University Sweden.
authors.forename: Gunilla Nordin
authors.initials: GN
authors.lastname: Fredrikson
authors.affiliation: Department of Medical Radiation Physics, Lund University Lund, Sweden.
authors.forename: Sven-Erik
authors.initials: SE
authors.lastname: Strand
keywords: Autoradiography; atherosclerosis; multi-radionuclide imaging; oxidized low density lipoprotein
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