Abstract
ObjectivesIt is necessary to develop a high-performance and biocompatible contrast agent to accurately diagnose various diseases via in vivo computed tomography (CT) imaging. Here, we synthesized a small molecular Bi-DOTA complex as a high-performance contrast agent for in vitro and in vivo CT bioimaging.Materials and MethodsIn our study, Bi-DOTA was fabricated through a facile and one-pot synthesis strategy. The formed Bi-DOTA complex was characterized via different techniques. Furthermore, Bi-DOTA was used for in vitro and in vivo CT bioimaging to verify its X-ray attenuation ability, especially in vivo kidney imaging, gastrointestinal tract CT imaging, and spectral CT imaging.ResultsA small molecular Bi-DOTA complex with a molecular mass of 0.61 kDa was synthesized successfully, which exhibited outstanding dispersion, good biocompatibility, and superior X-ray attenuation ability. Meanwhile, we showed that the obtained contrast agent was quite biocompatible and safe in the given concentration range as confirmed by in vitro and in vivo cytotoxicity assay. Also, the proposed contrast agent can be rapidly excreted from the body via the urinary system, avoiding the potential side effects caused by long-term retention in vivo. Importantly, Bi-DOTA was successfully used in high-quality in vitro CT imaging, in vivo kidney imaging, gastrointestinal tract CT imaging, and spectral CT imaging.ConclusionsThese superiorities allowed Bi-DOTA to be used as an efficient CT contrast agent and laid down a new way of designing high-performance CT contrast agents with great clinical transformation potential.
Highlights
Computed tomography (CT) is one of the most widely used imaging techniques in diagnostic medicine due to its high resolution, unlimited tissue penetration, and cost effectiveness [1,2,3,4,5]
Contrast agents can be divided into two major categories: small molecular agents and nanostructures containing high-Z elements [7], in which iodinated compounds are widely used as CT contrast agents
The Bi-DOTA was synthesized through a chelation of the Bi3+ and DOTA, as presented in Scheme 1
Summary
Computed tomography (CT) is one of the most widely used imaging techniques in diagnostic medicine due to its high resolution, unlimited tissue penetration, and cost effectiveness [1,2,3,4,5]. Clinically used iodinated small molecular agents (e.g., iohexol, ioversol, and iopamidol) suffer from low sensitivity, poor spectral CT, potential allergy, and renal toxicity [6, 8, 9] They are rapidly cleared via kidney, resulting in short circulation lifetime that limits their applications for CT angiography and CT perfusion imaging. It has been reported that the iodinated contrast agent is incorporated into polymers or polymer nanoparticles to extend the blood circulation time of the contrast agent, thereby realizing effective blood pool imaging [10,11,12,13] It is another obvious disadvantage that iodine has relatively low K-edge of (33 keV), which has a higher potential for damaging tissues [14]. It is critical but challenging to find a highperformance, biocompatible, low-cost, and safe contrast agent for enhanced CT and spectral CT imaging, as it may assist accurate diagnosis of various diseases and guide clinical treatment strategies
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