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Synthesis, Chemical Characterization and Multiscale Biological Evaluation of a dimericcRGD Peptide for Targeted Imaging of αVβ3 Integrin Activity
Abstrakt
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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Autorzy (14)
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Jamila Hedhli
- Beckman Institute for Advanced Science and Technology, Urbana, IL, USA
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Andrzej Czerwiński
- Peptides International Inc., Louisville, KY, USA
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Matthew Schuelke
- Beckman Institute for Advanced Science and Technology, Urbana, IL, USA
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Agata Płoska
- Medical University of Gdansk Department of Laboratory Diagnostics
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Lukas La Hood
- University of Illinois at Urbana-Champaign, Urbana, IL, USA Department of Bioengineering
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Spencer B. Mamer
- University of Illinois at Urbana-Champaign, Urbana, IL, USA Department of Bioengineering
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John A. Cole
- University of Illinois at Urbana-Champaign Department of Physics
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Paulina Czaplewska
- Intercollegiate Faculty of Biotechnology of the University of Gdansk and Medical University of Gdansk
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Maciej Banach
- Medical University of Lodz Department of Hypertension
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Iwona T. Dobrucki
- Beckman Institute for Advanced Science and Technology, Urbana, IL, USA
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Leszek Kalinowski
- Medical University of Gdansk, Gdansk, Department of Laboratory Diagnostics
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Princess Imoukhuede
- University of Illinois at Urbana-Champaign, Urbana, IL, USA Department of Bioengineering
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Lawrence W. Dobrucki
- Beckman Institute for Advanced Science and Technology, Urbana, IL, USA
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Pełna treść
- Wersja publikacji
- Accepted albo Published Version
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Informacje szczegółowe
- Kategoria:
- Publikacja w czasopiśmie
- Typ:
- artykuł w czasopiśmie wyróżnionym w JCR
- Opublikowano w:
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Scientific Reports
nr 7,
strony 1 - 15,
ISSN: 2045-2322 - Język:
- angielski
- Rok wydania:
- 2017
- Opis bibliograficzny:
- 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:
- Cyfrowy identyfikator dokumentu elektronicznego (otwiera się w nowej karcie) 10.1038/s41598-017-03224-8
- Weryfikacja:
- Politechnika Gdańska
wyświetlono 97 razy
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