Long-Circulating, Degradable Lanthanide-Based Contrast Agents for Pre-Clinical Microcomputed Tomography of the Vasculature
Abstract
Microcomputed tomography (micro-CT) is a micro-imaging modality used for small animal imaging given its high resolution, rapid scan times and quantifiable data. When studying soft tissues, a high-density material (contrast agent) is injected to help attenuate X-rays and provide contrast between these structures. Creation of new contrast agents is limited by short circulation times and localization in reticuloendothelial system (RES) organs. This thesis involves the development of two new contrast agents, which both employ tunable, degradable, self-immolative polymers (SIP). The first project studied a small library of poly(chelate) molecules with varying degradation rates. The second approach was based on PEtG-poly(ethylene glycol) (PEG) diblock copolymers that encapsulated 10 nm diameter nanoparticles. Both contrast agents were synthesized, and the poly(chelate) system was evaluated for in vivo efficacy. Overall results demonstrated successful prolonged vascular circulation along with excretion from the body over time by tuning the polymer’s molar mass and degradation rate.