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Am J Nucl Med Mol Imaging. 2014 Mar 20;4(2):172-80. eCollection 2014.

Multi-radionuclide digital autoradiography of the intra-aortic atherosclerotic plaques using a monoclonal antibody targeting oxidized low-density lipoprotein.

American journal of nuclear medicine and molecular imaging

Anders Orbom, Bo Jansson, Alexandru Schiopu, Susan Evans-Axelsson, Jan Nilsson, Gunilla Nordin Fredrikson, Sven-Erik Strand

Affiliations

  1. Department of Medical Radiation Physics, Lund University Lund, Sweden.
  2. Bioinvent International AB Lund, Sweden.
  3. Experimental Cardiovascular Research Unit, Department of Clinical Sciences, Skåne University Hospital Malmö, Lund University Sweden ; Cardiology Clinic, Skåne University Hospital Malmö Sweden.
  4. Division of Urological Cancers, Department of Clinical Sciences, Skåne University Hospital Malmö, Lund University Malmö, Sweden.
  5. Experimental Cardiovascular Research Unit, Department of Clinical Sciences, Skåne University Hospital Malmö, Lund University Sweden.

PMID: 24753983 PMCID: PMC3992210

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.

Keywords: Autoradiography; atherosclerosis; multi-radionuclide imaging; oxidized low density lipoprotein

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