Abstract
Computed tomography (CT) with contrast plays an important role as a clinical diagnostic tool but still has a limited diagnostic range. In this work, we developed a novel injectable iodine-based small molecule CT contrast agent, even can be used for bile duct diagnostics. The bile duct diagnosable CT contrast agent (BDICA) is synthesized with 5-amino-2,4,6-triiodoisophthaloyl dichloride (ATIPC), tromethamine and lactobionic acid (LBA) for asialoglycoprotein receptor (ASGPR) targeted delivery via receptor-mediated endocytosis and transport to the bile canaliculi. Specific binding to the ASGPRs was confirmed by in vitro cellular uptake in HepG2 cells (ASGPR positive) and HCT 116 cells (ASGPR negative). Compared to iohexol, BDICA has equal in vivo distribution and a 13-fold iodine increase in content was observed in bile juice after BDICA injection. The radiopaque contrast effect in the bile duct has been clearly shown in in vivo CT scans. Furthermore, within 36 h, 91.3% of the BDICA was eliminated without organ damage, which verified the overall safety of the contrast agent. BDICA not only provides sufficient contrast images similar to iohexol, but also provides superior images of the bile duct. Based on recent studies, it has been shown that BDICA is a promising, safe and effective contrast agent for CT imaging of the organs and soft tissues, including the bile duct.
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