Achieving safe and high-performance gastrointestinal tract spectral CT imaging with small-molecule lanthanide complex.

IF 8.1 Q1 ENGINEERING, BIOMEDICAL Biomaterials research Pub Date : 2023-11-22 DOI:10.1186/s40824-023-00463-x
Xiaoling Che, Chunmei Yang, Liping Pan, Didi Gu, Guidong Dai, Jian Shu, Lu Yang
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Abstract

Background: Non-intrusive imaging of gastrointestinal (GI) tract using computed tomography (CT) contrast agents is of the most significant issues in the diagnosis and treatment of GI diseases. Moreover, spectral CT, which can generate monochromatic images to display the X-ray attenuation characteristics of contrast agents, provides a better imaging sensitivity for diagnose inflammatory bowel disease (IBD) than convention CT imaging.

Methods: Herein, a convenient and one-pot synthesis method is provided for the fabrication of small-molecule lanthanide complex Holmium-tetraazacyclododecane-1, 4, 7, 10-tetraacetic acid (Ho-DOTA) as a biosafe and high-performance spectral CT contrast agent for GI imaging with IBD. In vivo CT imaging was administered with both healthy mice and colitis mice induced by dextran sodium sulfate.

Results: We found that Ho-DOTA accumulated in inflammation sites of large intestines and produced high CT contrast compared with healthy mice. Both in vitro and in vivo experimental results also showed that Ho-DOTA provided much more diagnostic sensitivity and accuracy due to the excellent X-ray attenuation characteristics of Ho-DOTA compared with clinical iodinate agent. Furthermore, the proposed contrast media could be timely excreted from the body via the urinary and digestive system, keeping away from the potential side effects due to long-term retention in vivo.

Conclusion: Accordingly, Ho-DOTA with excellent biocompatibility can be useful as a potential high-performance spectral CT contrast agent for further clinical imaging of gastrointestinal tract and diagnosis of intestinal system diseases.

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利用小分子镧系化合物实现安全、高效的胃肠道光谱CT成像。
背景:利用计算机断层扫描(CT)造影剂对胃肠道进行非侵入性成像是胃肠道疾病诊断和治疗中最重要的问题。此外,光谱CT可以生成单色图像来显示造影剂的x线衰减特征,对诊断炎症性肠病(IBD)提供了比常规CT更好的成像灵敏度。方法:本研究为制备小分子镧系配合物钬-四氮杂环十二烷- 1,4,7,10 -四乙酸(Ho-DOTA)提供了一种简便的一罐合成方法,该配合物可作为生物安全、高性能的IBD胃肠道成像光谱CT造影剂。对健康小鼠和右旋糖酐硫酸钠诱导的结肠炎小鼠进行体内CT成像。结果:我们发现Ho-DOTA在大肠炎症部位聚集,与健康小鼠相比具有较高的CT造影率。体外和体内实验结果也表明,由于Ho-DOTA良好的x射线衰减特性,与临床碘化剂相比,Ho-DOTA具有更高的诊断敏感性和准确性。此外,所提出的造影剂可以及时通过泌尿和消化系统排出体外,避免了由于在体内长期滞留而产生的潜在副作用。结论:Ho-DOTA具有良好的生物相容性,可作为一种潜在的高性能光谱CT造影剂,用于胃肠道的进一步临床成像和肠系统疾病的诊断。
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