Facile Hydrothermal Synthesis of an Iodine-Doped Computed Tomography Contrast Agent Using Insoluble Triiodobenzene

Carbonized iodine-doped particles (CIPs) were developed to overcome the disadvantages of computed tomography (CT) contrast agents, such as high osmolality and the radiodensity dilution of monomolecular contrast agents and low solubility and high toxicity of polymeric contrast agents. The CIPs were synthesized via a hydrothermal synthesis for 8 h using ATIPA (5-amino-2,4,6-triiodoisophthalic acid), glycerol, and tromethamine in the presence of D.W. (deionized water)-insoluble ATIPA converted into CIPs through a hydrothermal synthesis, showing high solubility and low osmotic pressure. The in vitro contrast effect determined for the resulting CIPs demonstrated a 57.6% enhancement compared to iohexol, and the osmotic pressure of the resulting CIPs was lower than that of iohexol. In addition, the CIPs demonstrated no dilution-induced contrast decrease in plasma and, therefore, demonstrated high contrast strength in vivo. Cytotoxicity tests, hemolysis assays, and histological analyses were conducted to verify the biocompatibility of the CIP product; however, no toxicity was observed. Furthermore, the CIP demonstrated a much higher contrast effect than iohexol at low concentrations. These results indicate that the CIP we have produced may be used as an effective blood pool agent for CT imaging.