The probe was used in vivo to image atherosclerotic plaques in living mice. The fluorescent probe is based on an activatable cell penetrating peptide (ACPP) that incorporates a peptide sequence from the proteinase activated receptor 1. The probe is preferentially cleaved by thrombin (cleavage can be blocked using thrombin inhibitors), and this fluorescent cleavage product builds up at the site of atherosclerotic lesions. The fluorescence intensity varies depending on the severity of the plaque and the histologic grade of the aorta.
The probe was also used with human atheroma specimens ex vivo, and the retention of the fluorescent cleavage product was 63% higher than that found when using a control ACPP.
The team hope that probes like this could eventually be used to deliver MRI contrast agents to atherosclerotic plaques to enable non-invasive detection of conditions by magnetic resonance imaging.
In vivo fluorescence imaging of atherosclerotic plaques with activatable cell-penetrating peptides targeting thrombin activity
Emilia S. Olson, Michael A. Whitney, Beth Friedman, Todd A. Aguilera, Jessica L. Crisp, Fred M. Baik, Tao Jiang, Stephen M. Baird, Sotirios Tsimikas, Roger Y. Tsien and Quyen T. Nguyen