Publications Repository - Gdańsk University of Technology

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.

Authors

• Jamila Hedhli,
• Andrzej Czerwiński,
• Matthew Schuelke,
• Agata Płoska,
• dr inż. Paweł Sowiński link open in new tab ,
• Lukas La Hood,
• Spencer B. Mamer,
• John A. Cole,
• Paulina Czaplewska,
• Maciej Banach,
• Iwona T. Dobrucki,
• Leszek Kalinowski,
• Princess Imoukhuede,
• Lawrence W. Dobrucki