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Sci Rep. 2017 Jun 9;7(1):3185. doi: 10.1038/s41598-017-03224-8.

Synthesis, Chemical Characterization and Multiscale Biological Evaluation of a Dimeric-cRGD Peptide for Targeted Imaging of α V β 3 Integrin Activity.

Author information

1
Beckman Institute for Advanced Science and Technology, Urbana, IL, USA.
2
Department of Bioengineering, University of Illinois at Urbana-Champaign, Urbana, IL, USA.
3
Peptides International Inc., Louisville, KY, USA.
4
Department of Laboratory Diagnostics, Medical University of Gdansk, Gdansk, Poland.
5
NMR Laboratory, Faculty of Chemistry, Gdansk University of Technology, Gdansk, Poland.
6
Department of Physics, University of Illinois at Urbana-Champaign, Urbana, IL, USA.
7
Intercollegiate Faculty of Biotechnology of the University of Gdansk and Medical University of Gdansk, Gdansk, Poland.
8
Department of Hypertension, Medical University of Lodz, Lodz, Poland.
9
Beckman Institute for Advanced Science and Technology, Urbana, IL, USA. dobrucki@illinois.edu.
10
Department of Bioengineering, University of Illinois at Urbana-Champaign, Urbana, IL, USA. dobrucki@illinois.edu.

Abstract

Cyclic peptides containing the Arg-Gly-Asp (RGD) sequence have been shown to specifically bind the angiogenesis biomarker α V β 3 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 β 3 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 β 3 in HUVECs (K d  ~ 35 nM). Dynamic PET-CT imaging indicated rapid blood clearance via kidney filtration, and accumulation within α V β 3-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 β 3 expression, both in vitro and in vivo.

PMID:
28600529
PMCID:
PMC5466598
DOI:
10.1038/s41598-017-03224-8
[Indexed for MEDLINE]
Free PMC Article

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