Non-cytotoxic, iodinated poly(ethylene oxide) (PEO) block-co-polymer contrast agents for computed tomography (CT) imaging

Abstract

Medical imaging techniques like X-ray, Magnetic Resonance Imaging (MRI), and Computed Tomography (CT) rely on contrast agents to enhance the visibility of blood vessels, tissues, and organs, making them crucial for medical diagnoses. Contrast agents used clinically are typically small molecules containing iodine, which are associated with nephrotoxicity, large dose requirements with potentially thyroid-disrupting levels of iodine, short half-lives, and are sometimes immunogenic. Loading/functionalization of larger molecules with iodine may attenuate X-rays similarly to small molecules, but at much lower concentrations, potentially mitigating the adverse effects of current contrast agents. To test this, iodinated poly(ethylene oxide) (PEO) was synthesized with varying amounts of iodine and structural features and examined for use as a contrast agent. First, 5 kg/mol PEG containing one terminal hydroxyl was reacted with trimethylaluminum to form a macroinitiator from which block-co-polymers consisting of PEO-co-poly(epichlorohydrin) (PECH) were synthesized with PECH blocks of 5, 15, and 30 kg/mol. The polymers were subsequently iodinated and characterized with 1H NMR and 13C NMR spectroscopy, size exclusion chromatography (SEC), and differential scanning calorimetry (DSC). X-ray attenuation was found to rival that of iohexol, a conventional contrast agent, at 1/20th the concentration. Further, we found that high molecular weight polymers were completely non-cytotoxic, unlike iohexol. These new materials hold promise as medical contrast agents.