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PET Imaging of Cardiac Wound Healing Using a Novel [68Ga]-Labeled NGR Probe in Rat Myocardial Infarction

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Abstract

Purpose

Peptides containing the asparagine-glycine-arginine (NGR) motif bind to aminopeptidase N (CD13), which is expressed on inflammatory cells, endothelial cells, and fibroblasts. It is unclear whether radiolabeled NGR-containing tracers could be used for in vivo imaging of the early wound-healing phase after myocardial infarction (MI) using positron emission tomography (PET).

Procedures

Uptake of novel tracer [68Ga]NGR was assessed together with [68Ga]arginine-glycine-aspartic acid ([68Ga]RGD) and 2-deoxy-2-[18 F]fluoro-d-glucose after myocardial ischemia/reperfusion (MI/R) injury using μ-PET and autoradiography, and relative expressions of CD13 and integrin β3 were assessed in fibroblasts, inflammatory cells, and endothelial cells by immunohistochemistry.

Results

In the infarcted myocardium, uptake of [68Ga]NGR was maximal from days 3 to 7 after MI/R, and correlated with fibroblast and inflammatory cell infiltration as well as [68Ga]RGD uptake.

Conclusions

[68Ga]NGR allows noninvasive and sequential determination of CD13 expression in fibroblasts and inflammatory cells by PET. This will facilitate monitoring of CD13 in the individual wound healing processes, allowing patient-specific therapies to improve outcome after MI.

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Abbreviations

MI:

Myocardial infarction

LV:

Left ventricular

NGR:

Asparagine-glycine-arginine

RGD:

Arginine-glycine-aspartic acid

[18 F]FDG:

2-Deoxy-2-[18 F]fluoro-d-glucose

P4H:

Prolyl-4-hydroxylase β

PET:

Positron emission tomography

NOTA:

1,4,7-Triazacyclononane-1,4,7-triacetic acid

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Acknowledgments

We gratefully acknowledge Annette Berbner, Charlotte Dienesch, Paula Arias, Katja Hirsch, and Annemieke Klan for expert technical assistance. This work was supported by grants from the Interdisciplinary Clinical Research Center Würzburg (to J.T., J.B. and S.S.: IZKF E-140).

Conflict of interest

The authors declare no conflict of interest.

Author information

Authors and Affiliations

  1. Department of Cardiology and Angiology, Hannover Medical School, Carl-Neuberg-Str. 1, 30625, Hannover, Germany

    Jochen Tillmanns, Daniela Fraccarollo & Johann Bauersachs

  2. Department of Nuclear Medicine, University Hospital Wurzburg, 97080, Wurzburg, Germany

    Magdalena Schneider, Dominik Richter & Samuel Samnick

  3. Department of Cardiothoracic Surgery, Hannover Medical School, 30625, Hannover, Germany

    Jan-Dieter Schmitto

  4. Institute for Pathology, Hannover Medical School, 30625, Hannover, Germany

    Florian Länger

Authors
  1. Jochen Tillmanns
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  2. Magdalena Schneider
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Correspondence to Jochen Tillmanns.

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The authors take responsibility for all aspects of the reliability and freedom from bias of the data presented and their discussed interpretation.

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Tillmanns, J., Schneider, M., Fraccarollo, D. et al. PET Imaging of Cardiac Wound Healing Using a Novel [68Ga]-Labeled NGR Probe in Rat Myocardial Infarction. Mol Imaging Biol 17, 76–86 (2015). https://doi.org/10.1007/s11307-014-0751-2

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  • DOI: https://doi.org/10.1007/s11307-014-0751-2

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