Positron Emission Tomography/Computed Tomographic and Magnetic Resonance Imaging in a Murine Model of Progressive Atherosclerosis Using 64Cu-Labeled Glycoprotein VI-Fc

Boris Bigalke*, Alkystis Phinikaridou, Marcelo E Andia, Margaret S Cooper, Andreas Schuster, Tanja Schönberger, Christoph M Griessinger, Thomas Wurster, David Onthank, Martin Ungerer, Meinrad Gawaz, Eike Nagel, Rene M Botnar

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

16 Citations (Scopus)

Abstract

Background—Plaque erosion leads to exposure of subendothelial collagen, which may be targeted by glycoprotein VI (GPVI). We aimed to detect plaque erosion using 64Cu-labeled GPVI-Fc.
Methods and Results—Four-week-old male Apolipoprotein E-deficient (ApoE-/-) mice (n=6) were fed a high-fat diet (HFD) for 12 weeks. C57BL/6J-wildtype (WT) mice served as controls (n=6). Another group of WT mice received a ligation injury of the left carotid artery (n=6) or sham procedure (n=4). All mice received a total activity of ~12MBq 64Cu-GPVI-Fc by tail vein injection followed by delayed (24h) positron emission tomography (PET) using a NanoPET/CT scanner (Mediso, Hungary; Bioscan, USA) with an acquisition time of 1800s. 72h after PET/CT, all mice were scanned 2h after intravenous administration of 0.2mmol/kg body weight of a gadolinium-based elastin-specific magnetic resonance contrast agent (ESMA). MRI was performed on a 3T clinical scanner (Philips Healthcare, Best, NL). In ApoE-/-mice, the 64Cu-GPVI-Fc uptake in the aortic arch was significantly higher compared to WT mice (ApoE-/-:13.2±1.5Bq/cm3vs.WT mice:5.1±0.5Bq/cm3;P=0.028). 64Cu-GPVI-Fc uptake was also higher in the injured left carotid artery wall compared to the intact right carotid artery of WT mice and as a trend compared to sham procedure (injured:20.7±1.3Bq/cm3vs.intact:2.3±0.5Bq/cm3;P=0.028;vs.sham:12.7±1.7Bq/cm3;P=0.068. Results were confirmed by ex-vivo histology and in-vivo MRI with ESMA that measures plaque burden and vessel wall remodeling. Higher R1 relaxation rates were found in the injured carotid wall with a T1-mapping sequence (injured:1.44±0.08s-1vs.intact:0.91±0.02s-1;P=0.028;vs.sham:0.97±0.05s-1;P=0.068) and in the aortic arch of ApoE-/-mice compared to WT mice (ApoE-/-:1.49±0.05s-1vs.WT:0.92±0.04s-1;P=0.028).
Conclusions—64Cu-GPVI-Fc PET imaging allows identification of exposed subendothelial collagen in injured WT and HFD fed ApoE-/-mice.
Original languageEnglish
Article numberN/A
Pages (from-to)957-964
Number of pages8
JournalCirculation-Cardiovascular imaging
Volume6
Issue number6
Early online date9 Oct 2013
DOIs
Publication statusPublished - Nov 2013

Keywords

  • atherosclerosis
  • magnetic resonance imaging
  • positron-emission tomography and computed tomography
  • PLATELET SCINTIGRAPHY
  • UNSTABLE PLAQUE
  • CONTRAST AGENT
  • APOE(-/-) MICE
  • PET
  • INFLAMMATION
  • AGGREGATION
  • BINDING

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