Chiral Gd-DOTA as a Versatile Platform for Hepatobiliary and Tumor Targeting MRI Contrast Agents

The leakage of gadolinium ions (Gd3+) from
commercial
Gd3+-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.

镓离子（Gd3+）从商用镓基对比剂（GBCAs）中的泄漏，目前已成为临床磁共振成像（MRI）扫描中的主要安全问题。缺乏特定任务专用型GBCAs限制了其在疾病早期检测及特定生物区域成像中的应用。本研究通过将手性Gd-DOTA的悬臂之一装饰上苯基类似物，构建了超稳定GBCAs，其稳定性常数高达27.08，在2年的1 M HCl溶液中几乎未发生去复合。筛选出的肝特异性手性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更加有利于手性Gd-DOTA作为肿瘤靶向探针。因此，鉴于其卓越的惰性，新型手性Gd-DOTA被认为是为各种临床目的设计下一代GBCAs的理想平台。