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Molecular Imaging and Biology

, Volume 19, Issue 1, pp 90–99 | Cite as

CD80 Is Upregulated in a Mouse Model with Shear Stress-Induced Atherosclerosis and Allows for Evaluating CD80-Targeting PET Tracers

  • Romana Meletta
  • Larissa Steier
  • Nicole Borel
  • Linjing Mu
  • Claudia Keller
  • Aristeidis Chiotellis
  • Erica Russo
  • Cornelia Halin
  • Simon M. Ametamey
  • Roger Schibli
  • Stefanie D. Krämer
  • Adrienne Müller Herde
Research Article

Abstract

Purpose

A shear stress-induced atherosclerosis mouse model was characterized for its expression of inflammation markers with focus on CD80. With this model, we evaluated two positron emission tomography (PET) radiotracers targeting CD80 as well as 2-deoxy-2-[18F]fluoro-d-mannose ([18F]FDM) in comparison with 2-deoxy-2-[18F]fluoro-d-glucose ([18F]FDG).

Procedure

A flow constrictive cuff implanted around the common carotid artery in apolipoprotein E knockout mice resulted in plaque formation. CD80 expression levels and plaque histopathology were evaluated. Serial PET/X-ray computed tomography scans were performed to follow inflammation.

Results

Plaque formation with increased levels of CD80 was observed. Histologically, plaques presented macrophage-rich and large necrotic areas covered by a thin fibrous cap. Of the CD80-specific tracers, one displayed an increased uptake in plaques by PET. Both [18F]FDG and [18F]FDM accumulated in atherosclerotic plaques.

Conclusion

This mouse model presented, similar to humans, an increased expression of CD80 which renders it suitable for non-invasively targeting CD80-positive immune cells and evaluating CD80-specific radiotracers.

Key words

Positron emission tomography Atherosclerosis CD80 ApoE KO Shear stress Plaque inflammation [18F]FDG 

Abbreviations

[18F]FDG

2-deoxy-2-[18F]fluoro-D-glucose

[18F]FDM

2-deoxy-2-[18F]fluoro-D-mannose

ApoE

Apolipoprotein E

DS

Downstream

FACS

Fluorescence-activated cell sorting

HFD

High-fat diet

KO

Knockout

ND

Normal diet

PET

Positron emission tomography

SUV

Standardized uptake value

US

Upstream

Notes

Acknowledgments

The authors thank Bruno Mancosu and Sabina Wunderlin for the technical support and helpful advice. We thank Dr. Michael Kuhlmann and Dirk Reinhardt from the European Institute for Molecular Imaging (EIMI, Münster, Germany) for introducing us to the shear stress-induced atherosclerosis mouse model and surgical training. We thank Dr. Cristina Müller (PSI, Villigen) for providing access to the Fuji ChemDri instrument and teaching sublingual blood collection. Ante Brekalo is acknowledged for the support in FDM synthesis. We appreciate the statistical advice by the statistical consultant of ETH. The authors acknowledge the support of the Scientific Center for Optical and Electron Microscopy (ScopeM) of the ETH Zurich. This work was financially supported by the Clinical Research Priority Program (CRPP) of the University of Zurich on Molecular Imaging (MINZ).

Author Contributions

R.M. conceived of and designed the experiments; established and performed all animal experiments, ex vivo staining, ex vivo PET, FACS, and qPCR; analyzed the data; and wrote the manuscript. L.S. performed the qPCR experiments and ex vivo staining and analyzed the data. N.B. supervised and analyzed the immunohistochemistry experiments. L.M. established the FDM chemistry and radiolabeling of 18F-FDM and was involved in the discussion of results. C.K. established and conducted all animal surgeries and in vivo PET scans. A.C. performed the organic synthesis of the AC74 precursor and reference compounds and radiolabeling of [18F]AC74. E.R. and C.H. conducted and analyzed the FACS experiments. S.M.A. and R.S. were involved in the discussion of results and revision of the manuscript. S.D.K. contributed to the supervision and planning of the experiments and revised the manuscript. A.M.H. supervised the study, experimental planning, and data interpretation and contributed to and supervised the manuscript writing.

Compliance with Ethical Standards

Conflict of Interest

The authors declare that they have no conflict of interest.

Supplementary material

11307_2016_987_MOESM1_ESM.pdf (2.2 mb)
ESM 1 (PDF 2.24 mb)

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Copyright information

© World Molecular Imaging Society 2016

Authors and Affiliations

  • Romana Meletta
    • 1
  • Larissa Steier
    • 1
  • Nicole Borel
    • 2
  • Linjing Mu
    • 3
  • Claudia Keller
    • 1
  • Aristeidis Chiotellis
    • 1
  • Erica Russo
    • 1
  • Cornelia Halin
    • 1
  • Simon M. Ametamey
    • 1
  • Roger Schibli
    • 1
    • 3
  • Stefanie D. Krämer
    • 1
  • Adrienne Müller Herde
    • 1
  1. 1.Department of Chemistry and Applied BiosciencesETH ZurichZurichSwitzerland
  2. 2.Institute of Veterinary Pathology, Vetsuisse FacultyUniversity of ZurichZurichSwitzerland
  3. 3.Department of Nuclear MedicineUniversity Hospital ZurichZurichSwitzerland

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