Lu Zhao,Li Ma,Xuetao Jia,Xiaoxue Wang,Wenjing Hou,Gang Shu,Bing Han,Dianxun Fu,Dong Li,Shao-Kai Sun,Jinbin Pan
Contrast-enhanced computed tomography perfusion (CTP) imaging is a critical clinical tool for evaluating cerebral blood flow after acute ischemic stroke (AIS), enabling accurate diagnosis and treatment planning. However, conventional iodine-based contrast agents may lead to allergic reactions and are contraindicated in patients with thyroid disorders. This study introduces Bi-DTPA dimeglumine, a renal-clearable and iodine-free bismuth chelate, for AIS perfusion assessment via CTP imaging. Bi-DTPA dimeglumine is synthesized through a simple and scalable process with nearly 100% yield (laboratory synthesis >100 g) and demonstrates excellent biocompatibility and efficient renal clearance. In a middle cerebral artery occlusion (MCAO) rat model, Bi-DTPA dimeglumine-enhanced CTP imaging accurately visualized vascular perfusion deficits, showing reduced cerebral blood volume (CBV) and cerebral blood flow (CBF), alongside prolonged time-to-maximum (Tmax) and mean transit time (MTT). Compared to iohexol, Bi-DTPA dimeglumine provided superior vascular contrast in computed tomography angiography (CTA), with contrast-to-noise ratio (CNR) improvements of 129.8 and 93.5% in normal and MCAO rats, respectively. Notably, CTP imaging revealed distinct reperfusion dynamics in ischemic regions postrecanalization. This iodine-free imaging agent marks a significant advancement in precise AIS diagnosis and post-treatment evaluation, addressing key limitations of existing contrast agents while enhancing diagnostic accuracy and safety.
Ma Li,Pan Jinbin,Shu Gang,Pan Haiyan,Li Jingang,Li Dong,Sun Shaokai
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.
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