Wenzhou Institute, University of Chinese Academy of Sciences, Wenzhou, Zhejiang 325000, China.
Oujiang Laboratory (Zhejiang Lab for Regenerative Medicine, Vision and Brain Health), Wenzhou, Zhejiang 325000, China.
J Med Chem. 2023 Nov 9;66(21):14669-14682. doi: 10.1021/acs.jmedchem.3c01183. Epub 2023 Oct 19.
The leakage of gadolinium ions (Gd) from commercial Gd-based contrast agents (GBCAs) in patients is currently the major safety concern in clinical magnetic resonance imaging (MRI) scans, and the lack of task-specific GBCAs limits its usage in the early detection of disease and imaging of specific biological regions. Herein, ultrastable GBCAs were constructed via decorating chiral Gd-DOTA with a phenylic analogue to one of the pendent arms, and the stability constant was determined as high as 27.08, accompanied by negligible decomplexation in 1 M of HCl over 2 years. A hepatic-specific chiral Gd-DOTA was screened out as a potential alternative to commercial Gd-EOB-DTPA, while combination with functional molecules favored chiral Gd-DOTA as tumor targeting probes. Therefore, the novel chiral Gd-DOTA is believed to be an ideal platform for designing the next generation of GBCAs for various clinical purposes due to its outstanding inert nature.
镧系元素钆离子（Gd）从商用基于钆的造影剂（GBCAs）中的泄漏，是目前临床磁共振成像（MRI）扫描中的主要安全关注点，而缺乏针对特定任务的 GBCAs 限制了其在疾病的早期检测和特定生物区域成像中的应用。在此，通过将手性 Gd-DOTA 与一个苯环类似物修饰到一个悬垂臂上，构建了超稳定的 GBCAs，其稳定常数高达 27.08，在 1 M 的 HCl 中 2 年内几乎没有脱配合物。筛选出一种肝特异性手性 Gd-DOTA 作为商业 Gd-EOB-DTPA 的潜在替代品，而与功能分子的结合则有利于手性 Gd-DOTA 作为肿瘤靶向探针。因此，由于其突出的惰性，新型手性 Gd-DOTA 有望成为设计用于各种临床用途的下一代 GBCAs 的理想平台。
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