Biodegradable iodinated polydisulfides as contrast agents for CT angiography

Current clinical CT contrast agents are mainly small molecular iodinated compounds, which often suffer from short blood pool retention for more comprehensive cardiovascular CT imaging and may cause contrast-induced nephropathy. In this work, we prepared polydisulfides containing a traditional iodinated CT contrast agent in order to optimize the pharmacokinetics of the agent and improve its safety. Initially acting as a macromolecular agent and achieving sharp blood vessel delineation, the polydisulfides can be reduced by endogenous thiols via disulfide-thiol exchange reaction to oligomers that can be readily excreted via renal filtration. Short polyethylene glycol (PEG) chain was also introduced to the polymers to further modify the in vivo properties of the agents. Strong and prolonged vascular enhancement has been generated with two new agents in mice (5-10 times higher blood pool enhancement than iodixanol). The polydisulfide agents gradually degraded and excreted via renal filtration. The gradual excretion process could prevent contrast-induced nephropathy. These results suggest that the biodegradable macromolecular CT contrast agents are promising safe and effective blood contrast agents for CT angiography and image-guided interventions.