Jeong Yohan, Na Kun
Department of Biotechnology, The Catholic University of Korea, 43 Jibong-ro, Wonmi-gu, Bucheon-si, Gyeonggi do 420-743 South Korea.
Biomater Res. 2018 Jun 13;22:17. doi: 10.1186/s40824-018-0127-9. eCollection 2018.
Gadolinium-based contrast agents are widely used as a contrast agent for magnetic resonance imaging. Since gadolinium ions are toxic, many chelators are developed to bind gadolinium ions to prevent free gadolinium-associated disease. However, many reports indicated that linear chelator-based contrast agents are associated with nephrogenic systemic fibrosis (NSF) in patients with low kidney function. Therefore, the demand for stable macrocyclic chelator-based contrast agent is now increasing.
1,4,7,10-Tetraazacyclododecane-1,4,7,10-tetraacetate (DOTA) was conjugated to lactobionic acid (LBA) through DCC-NHS coupling reaction. Gd (gadolinium ion) was chelated to 1,4,7,10-Tetraazacyclododecane-1,4,7,10-tetraacetate-lactobionic acid (DOTA-LAE) and free Gd was removed using a cation exchange column. In vitro cytotoxicity of contrast agent towards normal cells was measured using MTT assay. For in vivo MR imaging, contrast agents were intravenously injected to tumor-bearing mice and imaged by a MR imaging scanner.
This new macrocyclic gadolinium-based contrast agent showed enhanced in vitro paramagnetic properties compared to Gadovist. In addition, Gd-DOTA-LAE showed a 29% increased contrast enhancement of tumor tissue compared to normal tissue within 20 min past IV injection.
We developed a new macrocyclic T1-weighted MR contrast agent. This new contrast agent offers various opportunities for cancer detection and diagnosis.
钆基造影剂被广泛用作磁共振成像的造影剂。由于钆离子具有毒性,人们开发了许多螯合剂来结合钆离子,以预防与游离钆相关的疾病。然而,许多报告表明,基于线性螯合剂的造影剂与肾功能低下患者的肾源性系统性纤维化(NSF)有关。因此,目前对基于稳定大环螯合剂的造影剂的需求正在增加。
通过二环己基碳二亚胺- N-羟基琥珀酰亚胺(DCC-NHS)偶联反应,将1,4,7,10-四氮杂环十二烷-1,4,7,10-四乙酸(DOTA)与乳糖酸(LBA)偶联。将钆(钆离子)螯合到1,4,7,10-四氮杂环十二烷-1,4,7,10-四乙酸-乳糖酸(DOTA-LAE)上,并使用阳离子交换柱去除游离钆。使用MTT法测定造影剂对正常细胞的体外细胞毒性。对于体内磁共振成像,将造影剂静脉注射到荷瘤小鼠体内,并通过磁共振成像扫描仪进行成像。
与钆特酸相比,这种新型大环钆基造影剂在体外显示出增强的顺磁特性。此外,与静脉注射后20分钟内的正常组织相比,钆- DOTA-LAE显示肿瘤组织的对比增强增加了29%。
我们开发了一种新型大环T1加权磁共振造影剂。这种新型造影剂为癌症检测和诊断提供了各种机会。