Synthesis, Chemical Characterization and Multiscale Biological Evaluation of a dimericcRGD Peptide for Targeted Imaging of αVβ3 Integrin Activity - Publication - Bridge of Knowledge

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Synthesis, Chemical Characterization and Multiscale Biological Evaluation of a dimericcRGD Peptide for Targeted Imaging of αVβ3 Integrin Activity

Abstract

Cyclic peptides containing the Arg-Gly-Asp (RGD) sequence have been shown to specifically bind the angiogenesis biomarker α V β3 integrin. We report the synthesis, chemical characterization, and biological evaluation of two novel dimeric cyclic RGD-based molecular probes for the targeted imaging of α V β3 activity (a radiolabeled version, 64Cu-NOTA-PEG4-cRGD2, for PET imaging, and a fluorescent version, FITC-PEG4-cRGD2, for in vitro work). We investigated the performance of this probe at the receptor, cell, organ, and whole-body levels, including its use to detect diabetes associated impairment of ischemia-induced myocardial angiogenesis. Both versions of the probe were found to be stable, demonstrated fast receptor association constants, and showed high specificity for α V β3 in HUVECs (K d  ~ 35 nM). Dynamic PET-CT imaging indicated rapid blood clearance via kidney filtration, and accumulation within α V β3-positive infarcted myocardium. 64Cu-NOTA-PEG4-cRGD2 demonstrated a favorable biodistribution, slow washout, and excellent performance with respect to the quality of the PET-CT images obtained. Importantly, the ratio of probe uptake in infarcted heart tissue compared to normal tissue was significantly higher in non-diabetic rats than in diabetic ones. Overall, our probes are promising agents for non-invasive quantitative imaging of α V β3 expression, both in vitro and in vivo.

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Authors (14)

  • Photo of Jamila Hedhli

    Jamila Hedhli

    • Beckman Institute for Advanced Science and Technology, Urbana, IL, USA
  • Photo of Andrzej Czerwiński

    Andrzej Czerwiński

    • Peptides International Inc., Louisville, KY, USA
  • Photo of Matthew Schuelke

    Matthew Schuelke

    • Beckman Institute for Advanced Science and Technology, Urbana, IL, USA
  • Photo of Agata Płoska

    Agata Płoska

    • Medical University of Gdansk Department of Laboratory Diagnostics
  • Photo of dr inż. Paweł Sowiński

    Paweł Sowiński dr inż.

  • Photo of Lukas La Hood

    Lukas La Hood

    • University of Illinois at Urbana-Champaign, Urbana, IL, USA Department of Bioengineering
  • Photo of Spencer B. Mamer

    Spencer B. Mamer

    • University of Illinois at Urbana-Champaign, Urbana, IL, USA Department of Bioengineering
  • Photo of John A. Cole

    John A. Cole

    • University of Illinois at Urbana-Champaign Department of Physics
  • Photo of Paulina Czaplewska

    Paulina Czaplewska

    • Intercollegiate Faculty of Biotechnology of the University of Gdansk and Medical University of Gdansk
  • Photo of Maciej Banach

    Maciej Banach

    • Medical University of Lodz Department of Hypertension
  • Photo of Iwona T. Dobrucki

    Iwona T. Dobrucki

    • Beckman Institute for Advanced Science and Technology, Urbana, IL, USA
  • Photo of Leszek Kalinowski

    Leszek Kalinowski

    • Medical University of Gdansk, Gdansk, Department of Laboratory Diagnostics
  • Photo of Princess Imoukhuede

    Princess Imoukhuede

    • University of Illinois at Urbana-Champaign, Urbana, IL, USA Department of Bioengineering
  • Photo of Lawrence W. Dobrucki

    Lawrence W. Dobrucki

    • Beckman Institute for Advanced Science and Technology, Urbana, IL, USA

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Category:
Articles
Type:
artykuł w czasopiśmie wyróżnionym w JCR
Published in:
Scientific Reports no. 7, pages 1 - 15,
ISSN: 2045-2322
Language:
English
Publication year:
2017
Bibliographic description:
Hedhli J., Czerwiński A., Schuelke M., Płoska A., Sowiński P., La Hood L., Mamer S., Cole J., Czaplewska P., Banach M., Dobrucki I., Kalinowski L., Imoukhuede P., Dobrucki L.: Synthesis, Chemical Characterization and Multiscale Biological Evaluation of a dimericcRGD Peptide for Targeted Imaging of αVβ3 Integrin Activity// Scientific Reports. -Vol. 7, (2017), s.1-15
DOI:
Digital Object Identifier (open in new tab) 10.1038/s41598-017-03224-8
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