Non-invasive fast assessment of hepatic injury through computed tomography imaging with renal-clearable Bi-DTPA dimeglumine

Abstract

Enhanced computed tomography (CT) imaging with iodinated imaging probes is widely utilized for the diagnosis and evaluation of various liver diseases. However, these iodine-based imaging probes face intractable limitations including allergic reactions and contraindications. Herein, we propose the utilization of renal-clearable iodine-free bismuth chelate (Bi-DTPA dimeglumine) for the non-invasive fast assessment of hepatic ischemia-reperfusion injury (HIRI) via CT imaging for the first time. Bi-DTPA dimeglumine offers several advantages such as simple synthesis, no purification requirement, a yield approaching 100%, large-scale production capability (laboratory synthesis > 100 g), excellent biocompatibility, and superior CT imaging performance. In a normal rat model, the administration of Bi-DTPA dimeglumine resulted in a significant 63.79% increase in liver CT value within a very short time period (30 s). Furthermore, in a HIRI rat model, Bi-DTPA dimeglumine enabled the rapid differentiation between healthy and injured areas based on the notable disparity in liver CT values as early as 15 min post-reperfusion, which showed a strong correlation with the histopathological analysis results. Additionally, Bi-DTPA dimeglumine can be almost eliminated from the body via the kidneys within 24 h. As an inherently advantageous alternative to iodinated imaging probes, Bi-DTPA dimeglumine exhibits promising prospects for application in liver disease diagnosis.