Intravascular Molecular Imaging of Stent Healing Using A Peptide-Based Fibrin-Targeting Fluorescent Probe

Catherine Hagearty-Mattern

Faculty: Narayan Sharma and Lauren Endres

Our group proposed an innovative methodology using fluorescence agents to detect fibrin accumulation in blood clots at the point of care during a percutaneous coronary intervention (PCI). Currently, a limited amount of fluorescence agents are available for NIRF imaging. The synthetic methods for fluorescence agents are inefficient, resulting in low yields and the degradation of fluorescent dyes.

Thus, there is a tremendous need for a better method of synthesizing fibrin-targeted NIRF thrombus imaging agents. Through the cyclization of a linear peptide via disulfide bond formation induced by sonication, we developed a new technique for synthesizing a fibrin-targeted NIRF thrombus imaging agent, termed FTP11-CyAl5.5.

First, using an automated peptide synthesizer, we prepared the FTP11 peptide. Afterward, we labeled the peptide with the cyanine dye CyAl5.5 and triethylamine in dimethylformamide, followed by the cleaving of FTP11-CyAl5.5 from the resin.

Then, macrocyclization via disulfide bond formation was induced using ultrasonic irradiation. The synthesis was then performed with another fluorescent dye, AF555, to make FTP11-AF555. ESI-MS and analytical HPLC were used to monitor the reaction, and the yields and efficiency of our novel technique were compared to current synthetic methods of in-solution cyclization and on-resin chemistries.