A Protease-Activatable Nanoparticle Contrast Agent for Molecular Imaging by Dual Energy Computed Tomography

Jeffrey Ashton1, Cristian Badea2, Jennifer West1 1Duke University, Biomedical Engineering Department 2Duke University Medical Center, Department of Radiology Statement of Purpose: X-ray computed tomography (CT) is one of the most useful imaging tools for modern clinicians. However, molecular imaging with CT is not feasible with existing contrast agents, so clinicians must instead rely on other modalities which are more expensive and less readily available. Dual energy CT, a relatively new technique using two x-ray energies for a single scan, can provide valuable information about material composition. We have previously shown that dual energy CT can accurately differentiate and quantify gold and iodine in vivo1 (see Fig. 1). Two-material differentiation can potentially be used for molecular imaging if it is coupled with appropriately-designed contrast agents. We seek to develop for the first time an activatable dual energy CT contrast agent for the molecular imaging of protease activity. This agent is a composite probe consisting of iodine-containing liposomes (~120 nm) linked to multiple small (~5 nm) gold nanoparticles (AuNPs) by a protease-cleavable peptide. Cleavage of the peptide within tumor tissues will allow the small AuNPs to diffuse away from the much larger liposomes. Separation of the gold and iodine signals, detected by dual energy CT, can then be used to measure protease activity.